1-{3-[(7-Fluoro-9H-pyrimido[4,5-b]indol-4-yl)(meth­yl)amino]­piperidin-1-yl}propan-1-one

The title compound, C₁₉H₂₂FN₅O, has been synthesized as an inhibitor of glycogen synthase kinase-3β. Two mol­ecules inter­act via two N—H...N hydrogen bonds, forming centrosymmetric dimers.

Key indicators

• Single-crystal X-ray study
• T = 120 K
• Mean [sigma](C-C) = 0.004 Å
• R factor = 0.069
• wR factor = 0.194
• Data-to-parameter ratio = 17.7

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT906_ALERT_3_C Large K Value in the Analysis of Variance ......      3.543 Check
PLAT911_ALERT_3_C Missing FCF Refl Between Thmin & STh/L=    0.600         20 Report
PLAT918_ALERT_3_C Reflection(s) with I(obs) much Smaller I(calc) .          2 Check
PLAT934_ALERT_3_C Number of (Iobs-Icalc)/Sigma(W) > 10 Outliers ..          1 Check

Alert level G
PLAT007_ALERT_5_G Number of Unrefined Donor-H Atoms ..............          1 Report
PLAT793_ALERT_4_G Model has Chirality at C16         (Centro SPGR)          S Verify
PLAT910_ALERT_3_G Missing # of FCF Reflection(s) Below Theta(Min).          1 Note
PLAT912_ALERT_4_G Missing # of FCF Reflections Above STh/L=  0.600         20 Note
PLAT955_ALERT_1_G Reported (CIF) and Actual (FCF) Lmax Differ by .          1 Units
PLAT978_ALERT_2_G Number C-C Bonds with Positive Residual Density.          2 Info

   0 ALERT level A = Most likely a serious problem - resolve or explain
   0 ALERT level B = A potentially serious problem, consider carefully
   4 ALERT level C = Check. Ensure it is not caused by an omission or oversight
   6 ALERT level G = General information/check it is not something unexpected

   1 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   1 ALERT type 2 Indicator that the structure model may be wrong or deficient
   5 ALERT type 3 Indicator that the structure quality may be low
   2 ALERT type 4 Improvement, methodology, query or suggestion
   1 ALERT type 5 Informative message, check

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Computing details

Data collection: X-AREA WinXpose (Stoe & Cie, 2019); cell refinement: X-AREA Recipe (Stoe & Cie, 2019); data reduction: X-AREA Integrate (Stoe & Cie, 2019); program(s) used to solve structure: SHELXT2014 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018/3 (Sheldrick, 2015b).

1-{3-[(7-Fluoro-9H-pyrimido[4,5-b]indol-4-yl)(methyl)amino]piperidin-1-yl}propan-1-one

Crystal data

C19H22FN5O	Dx = 1.326 Mg m^−3
Mr = 355.41	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, Pbca	Cell parameters from 7975 reflections
a = 10.6982 (3) Å	θ = 2.4–28.3°
b = 19.8473 (8) Å	µ = 0.09 mm^−1
c = 16.7642 (6) Å	T = 120 K
V = 3559.5 (2) Å^3	Block, colourless
Z = 8	0.35 × 0.17 × 0.08 mm
F(000) = 1504

Data collection

Stoe IPDS 2T diffractometer	2840 reflections with I > 2σ(I)
Radiation source: sealed X-ray tube, 12 x 0.4 mm long-fine focus	Rint = 0.066
Detector resolution: 6.67 pixels mm^-1	θmax = 27.9°, θmin = 2.4°
rotation method, ω scans	h = −14→12
9882 measured reflections	k = −22→26
4202 independent reflections	l = −19→22

Refinement

Refinement on F^2	Primary atom site location: dual
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.069	H-atom parameters constrained
wR(F^2) = 0.194	w = 1/[σ^2(Fo^2) + (0.0822P)^2 + 2.3561P] where P = (Fo^2 + 2Fc^2)/3
S = 1.14	(Δ/σ)max = 0.001
4202 reflections	Δρmax = 0.36 e Å^−3
237 parameters	Δρmin = −0.41 e Å^−3
0 restraints

Special details

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. H atoms found in a difference map. Then, they were positioned geometrically and refined using a riding model with C—H = 0.95 Å and U_iso(H) = 1.2Ueq(C) for aromatic CH, C—H = 0.99 Å and U_iso(H) = 1.2Ueq(C) for CH₂, C—H = 1.00 Å and U_iso(H) = 1.2Ueq(C) for tertiary H and with C—H = 0.98 Å and U_iso(H) = 1.5Ueq(C) for CH₃. The methyl groups were allowed to rotate but not to tip.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
F1	0.03835 (15)	0.75389 (8)	0.26711 (10)	0.0344 (4)
N1	0.0797 (2)	0.56013 (11)	0.43722 (12)	0.0247 (5)
H1	0.011506	0.562102	0.466503	0.030*
C2	0.1147 (2)	0.60634 (12)	0.38014 (14)	0.0224 (5)
C3	0.0481 (2)	0.66282 (13)	0.35527 (14)	0.0243 (5)
H3	−0.028161	0.676063	0.379652	0.029*
C4	0.1002 (2)	0.69815 (13)	0.29309 (15)	0.0260 (5)
C5	0.2099 (3)	0.67981 (13)	0.25432 (16)	0.0272 (5)
H5	0.239394	0.705203	0.210137	0.033*
C6	0.2757 (2)	0.62393 (13)	0.28097 (15)	0.0259 (5)
H6	0.351084	0.610925	0.255311	0.031*
C7	0.2302 (2)	0.58663 (12)	0.34613 (14)	0.0221 (5)
C8	0.2673 (2)	0.52527 (12)	0.38809 (14)	0.0213 (5)
C9	0.3654 (2)	0.47773 (12)	0.38893 (14)	0.0218 (5)
N10	0.3530 (2)	0.42059 (11)	0.43277 (13)	0.0255 (5)
C11	0.2515 (2)	0.41287 (13)	0.47767 (15)	0.0256 (5)
H11	0.245845	0.371894	0.506735	0.031*
N12	0.15664 (19)	0.45588 (11)	0.48670 (12)	0.0250 (5)
C13	0.1679 (2)	0.51100 (13)	0.44078 (14)	0.0230 (5)
N14	0.47433 (18)	0.48402 (10)	0.34654 (12)	0.0225 (4)
C15	0.5310 (2)	0.54981 (13)	0.33467 (16)	0.0283 (6)
H15A	0.612776	0.551050	0.360984	0.042*
H15B	0.476882	0.584631	0.357578	0.042*
H15C	0.541595	0.558115	0.277441	0.042*
C16	0.5572 (2)	0.42482 (13)	0.34154 (15)	0.0252 (5)
H16	0.503095	0.383843	0.338129	0.030*
C17	0.6387 (3)	0.42663 (14)	0.26687 (16)	0.0289 (6)
H17A	0.691916	0.467432	0.267526	0.035*
H17B	0.585136	0.428388	0.218752	0.035*
C18	0.7214 (3)	0.36317 (14)	0.26433 (16)	0.0308 (6)
H18A	0.668171	0.322908	0.256490	0.037*
H18B	0.779753	0.366247	0.218634	0.037*
C19	0.7956 (2)	0.35565 (14)	0.34126 (15)	0.0291 (6)
H19A	0.842958	0.312818	0.340020	0.035*
H19B	0.856282	0.393090	0.345791	0.035*
N20	0.7121 (2)	0.35610 (11)	0.41082 (13)	0.0275 (5)
C21	0.6384 (2)	0.41798 (13)	0.41636 (15)	0.0272 (6)
H21A	0.694825	0.457341	0.420976	0.033*
H21B	0.584720	0.416496	0.464414	0.033*
C22	0.6811 (2)	0.29723 (13)	0.44725 (15)	0.0261 (5)
O23	0.72866 (19)	0.24321 (10)	0.42863 (11)	0.0328 (5)
C24	0.5879 (3)	0.30135 (14)	0.51579 (16)	0.0317 (6)
H24A	0.610597	0.339869	0.550410	0.038*
H24B	0.503685	0.310256	0.493727	0.038*
C25	0.5829 (3)	0.23828 (16)	0.56585 (18)	0.0421 (8)
H25A	0.554350	0.200474	0.532942	0.063*
H25B	0.524624	0.244955	0.610271	0.063*
H25C	0.666367	0.228412	0.586876	0.063*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
F1	0.0314 (8)	0.0340 (9)	0.0379 (9)	0.0069 (7)	0.0044 (7)	0.0117 (7)
N1	0.0215 (10)	0.0274 (11)	0.0252 (10)	0.0027 (9)	0.0058 (8)	0.0051 (8)
C2	0.0205 (11)	0.0266 (13)	0.0202 (11)	0.0000 (10)	0.0010 (9)	0.0013 (9)
C3	0.0201 (11)	0.0290 (13)	0.0238 (12)	−0.0001 (10)	0.0015 (10)	−0.0001 (10)
C4	0.0242 (12)	0.0254 (13)	0.0285 (12)	0.0026 (10)	−0.0004 (10)	0.0052 (10)
C5	0.0257 (13)	0.0279 (13)	0.0279 (13)	−0.0023 (11)	0.0026 (10)	0.0062 (10)
C6	0.0198 (12)	0.0311 (14)	0.0267 (12)	−0.0010 (10)	0.0048 (10)	0.0042 (10)
C7	0.0200 (11)	0.0243 (12)	0.0220 (11)	−0.0020 (9)	0.0009 (9)	−0.0014 (9)
C8	0.0177 (11)	0.0255 (12)	0.0207 (11)	0.0003 (9)	0.0004 (9)	0.0011 (9)
C9	0.0181 (11)	0.0262 (12)	0.0210 (11)	−0.0019 (10)	0.0000 (9)	−0.0005 (9)
N10	0.0202 (10)	0.0286 (11)	0.0276 (11)	0.0000 (9)	0.0027 (8)	0.0040 (8)
C11	0.0209 (11)	0.0300 (14)	0.0260 (12)	−0.0015 (10)	0.0013 (10)	0.0048 (10)
N12	0.0215 (10)	0.0268 (11)	0.0268 (11)	−0.0005 (9)	0.0029 (8)	0.0049 (8)
C13	0.0176 (11)	0.0293 (14)	0.0220 (12)	−0.0016 (10)	−0.0005 (9)	0.0004 (9)
N14	0.0174 (10)	0.0234 (11)	0.0266 (10)	−0.0002 (8)	0.0038 (8)	0.0002 (8)
C15	0.0212 (12)	0.0285 (14)	0.0352 (14)	−0.0009 (10)	0.0026 (11)	0.0026 (11)
C16	0.0204 (12)	0.0285 (13)	0.0266 (12)	0.0023 (10)	0.0032 (10)	0.0004 (10)
C17	0.0276 (13)	0.0321 (14)	0.0269 (13)	0.0036 (11)	0.0057 (11)	0.0041 (10)
C18	0.0299 (14)	0.0337 (15)	0.0288 (13)	0.0047 (12)	0.0072 (11)	−0.0003 (11)
C19	0.0244 (12)	0.0332 (14)	0.0299 (13)	0.0020 (11)	0.0075 (10)	0.0008 (11)
N20	0.0242 (11)	0.0306 (12)	0.0277 (11)	0.0049 (9)	0.0029 (9)	−0.0007 (9)
C21	0.0241 (12)	0.0295 (14)	0.0279 (13)	0.0018 (10)	−0.0003 (10)	−0.0004 (10)
C22	0.0239 (12)	0.0298 (14)	0.0246 (12)	0.0007 (10)	−0.0011 (10)	−0.0006 (10)
O23	0.0362 (11)	0.0302 (10)	0.0320 (10)	0.0063 (9)	0.0065 (8)	0.0003 (8)
C24	0.0318 (14)	0.0364 (15)	0.0270 (13)	0.0003 (12)	0.0057 (11)	−0.0014 (11)
C25	0.0496 (19)	0.0461 (19)	0.0305 (15)	0.0016 (15)	0.0114 (13)	0.0051 (13)

Geometric parameters (Å, º)

F1—C4	1.361 (3)	C15—H15C	0.9800
N1—C13	1.359 (3)	C16—C17	1.526 (3)
N1—C2	1.377 (3)	C16—C21	1.532 (4)
N1—H1	0.8800	C16—H16	1.0000
C2—C3	1.392 (3)	C17—C18	1.540 (4)
C2—C7	1.417 (3)	C17—H17A	0.9900
C3—C4	1.375 (3)	C17—H17B	0.9900
C3—H3	0.9500	C18—C19	1.522 (4)
C4—C5	1.389 (4)	C18—H18A	0.9900
C5—C6	1.388 (4)	C18—H18B	0.9900
C5—H5	0.9500	C19—N20	1.469 (3)
C6—C7	1.406 (3)	C19—H19A	0.9900
C6—H6	0.9500	C19—H19B	0.9900
C7—C8	1.461 (3)	N20—C22	1.360 (3)
C8—C13	1.411 (3)	N20—C21	1.462 (3)
C8—C9	1.411 (3)	C21—H21A	0.9900
C9—N10	1.358 (3)	C21—H21B	0.9900
C9—N14	1.370 (3)	C22—O23	1.227 (3)
N10—C11	1.330 (3)	C22—C24	1.523 (4)
C11—N12	1.335 (3)	C24—C25	1.508 (4)
C11—H11	0.9500	C24—H24A	0.9900
N12—C13	1.343 (3)	C24—H24B	0.9900
N14—C15	1.453 (3)	C25—H25A	0.9800
N14—C16	1.474 (3)	C25—H25B	0.9800
C15—H15A	0.9800	C25—H25C	0.9800
C15—H15B	0.9800
C13—N1—C2	108.6 (2)	C17—C16—C21	110.5 (2)
C13—N1—H1	125.7	N14—C16—H16	107.6
C2—N1—H1	125.7	C17—C16—H16	107.6
N1—C2—C3	127.3 (2)	C21—C16—H16	107.6
N1—C2—C7	109.4 (2)	C16—C17—C18	109.4 (2)
C3—C2—C7	123.2 (2)	C16—C17—H17A	109.8
C4—C3—C2	115.5 (2)	C18—C17—H17A	109.8
C4—C3—H3	122.2	C16—C17—H17B	109.8
C2—C3—H3	122.2	C18—C17—H17B	109.8
F1—C4—C3	117.4 (2)	H17A—C17—H17B	108.2
F1—C4—C5	118.3 (2)	C19—C18—C17	110.9 (2)
C3—C4—C5	124.3 (2)	C19—C18—H18A	109.5
C6—C5—C4	119.2 (2)	C17—C18—H18A	109.5
C6—C5—H5	120.4	C19—C18—H18B	109.5
C4—C5—H5	120.4	C17—C18—H18B	109.5
C5—C6—C7	119.7 (2)	H18A—C18—H18B	108.1
C5—C6—H6	120.1	N20—C19—C18	110.8 (2)
C7—C6—H6	120.1	N20—C19—H19A	109.5
C6—C7—C2	118.0 (2)	C18—C19—H19A	109.5
C6—C7—C8	136.0 (2)	N20—C19—H19B	109.5
C2—C7—C8	105.9 (2)	C18—C19—H19B	109.5
C13—C8—C9	114.8 (2)	H19A—C19—H19B	108.1
C13—C8—C7	105.3 (2)	C22—N20—C21	124.2 (2)
C9—C8—C7	139.8 (2)	C22—N20—C19	120.0 (2)
N10—C9—N14	116.1 (2)	C21—N20—C19	112.5 (2)
N10—C9—C8	119.4 (2)	N20—C21—C16	109.1 (2)
N14—C9—C8	124.5 (2)	N20—C21—H21A	109.9
C11—N10—C9	118.8 (2)	C16—C21—H21A	109.9
N10—C11—N12	127.7 (2)	N20—C21—H21B	109.9
N10—C11—H11	116.2	C16—C21—H21B	109.9
N12—C11—H11	116.2	H21A—C21—H21B	108.3
C11—N12—C13	112.8 (2)	O23—C22—N20	122.4 (2)
N12—C13—N1	123.2 (2)	O23—C22—C24	120.7 (2)
N12—C13—C8	126.2 (2)	N20—C22—C24	116.9 (2)
N1—C13—C8	110.6 (2)	C25—C24—C22	113.5 (2)
C9—N14—C15	120.5 (2)	C25—C24—H24A	108.9
C9—N14—C16	117.9 (2)	C22—C24—H24A	108.9
C15—N14—C16	117.21 (19)	C25—C24—H24B	108.9
N14—C15—H15A	109.5	C22—C24—H24B	108.9
N14—C15—H15B	109.5	H24A—C24—H24B	107.7
H15A—C15—H15B	109.5	C24—C25—H25A	109.5
N14—C15—H15C	109.5	C24—C25—H25B	109.5
H15A—C15—H15C	109.5	H25A—C25—H25B	109.5
H15B—C15—H15C	109.5	C24—C25—H25C	109.5
N14—C16—C17	111.8 (2)	H25A—C25—H25C	109.5
N14—C16—C21	111.4 (2)	H25B—C25—H25C	109.5
C13—N1—C2—C3	177.1 (2)	C2—N1—C13—C8	2.7 (3)
C13—N1—C2—C7	−0.5 (3)	C9—C8—C13—N12	−3.8 (4)
N1—C2—C3—C4	−175.6 (2)	C7—C8—C13—N12	174.0 (2)
C7—C2—C3—C4	1.7 (4)	C9—C8—C13—N1	178.6 (2)
C2—C3—C4—F1	−179.8 (2)	C7—C8—C13—N1	−3.6 (3)
C2—C3—C4—C5	1.7 (4)	N10—C9—N14—C15	−146.1 (2)
F1—C4—C5—C6	178.7 (2)	C8—C9—N14—C15	35.4 (3)
C3—C4—C5—C6	−2.7 (4)	N10—C9—N14—C16	9.8 (3)
C4—C5—C6—C7	0.4 (4)	C8—C9—N14—C16	−168.7 (2)
C5—C6—C7—C2	2.7 (4)	C9—N14—C16—C17	154.3 (2)
C5—C6—C7—C8	176.5 (3)	C15—N14—C16—C17	−49.0 (3)
N1—C2—C7—C6	173.9 (2)	C9—N14—C16—C21	−81.5 (3)
C3—C2—C7—C6	−3.9 (4)	C15—N14—C16—C21	75.2 (3)
N1—C2—C7—C8	−1.7 (3)	N14—C16—C17—C18	−179.1 (2)
C3—C2—C7—C8	−179.4 (2)	C21—C16—C17—C18	56.2 (3)
C6—C7—C8—C13	−171.2 (3)	C16—C17—C18—C19	−54.0 (3)
C2—C7—C8—C13	3.1 (3)	C17—C18—C19—N20	54.8 (3)
C6—C7—C8—C9	5.8 (5)	C18—C19—N20—C22	101.4 (3)
C2—C7—C8—C9	−179.9 (3)	C18—C19—N20—C21	−58.9 (3)
C13—C8—C9—N10	6.0 (3)	C22—N20—C21—C16	−98.9 (3)
C7—C8—C9—N10	−170.8 (3)	C19—N20—C21—C16	60.4 (3)
C13—C8—C9—N14	−175.5 (2)	N14—C16—C21—N20	176.0 (2)
C7—C8—C9—N14	7.7 (5)	C17—C16—C21—N20	−59.1 (3)
N14—C9—N10—C11	177.4 (2)	C21—N20—C22—O23	164.3 (2)
C8—C9—N10—C11	−4.0 (4)	C19—N20—C22—O23	6.4 (4)
C9—N10—C11—N12	−1.0 (4)	C21—N20—C22—C24	−18.4 (4)
N10—C11—N12—C13	3.2 (4)	C19—N20—C22—C24	−176.4 (2)
C11—N12—C13—N1	176.8 (2)	O23—C22—C24—C25	11.8 (4)
C11—N12—C13—C8	−0.6 (4)	N20—C22—C24—C25	−165.5 (3)
C2—N1—C13—N12	−175.1 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···N12^i	0.88	1.99	2.849 (3)	164
C5—H5···O23^ii	0.95	2.47	3.380 (3)	161
C11—H11···O23^iii	0.95	2.54	3.482 (3)	174
C19—H19A···O23	0.99	2.37	2.764 (3)	103
C19—H19A···F1^iv	0.99	2.49	3.246 (3)	133

Symmetry codes: (i) −x, −y+1, −z+1; (ii) −x+1, y+1/2, −z+1/2; (iii) x−1/2, −y+1/2, −z+1; (iv) −x+1, y−1/2, −z+1/2.