4-Amino-1-methylpiperidine → 4-(9-Cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methyl-N-(1-methylpiperidin-4-yl)benzamide

HRID 1880850Notes

Reaction equation

HRID 1880850 reaction equation
[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26]([OH:28])=O)=[CH:24][C:23]=4[CH3:31])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:56][N:57]1[CH2:62][CH2:61][CH:60]([NH2:63])[CH2:59][CH2:58]1>>[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26]([NH:63][CH:60]5[CH2:61][CH2:62][N:57]([CH3:56])[CH2:58][CH2:59]5)=[O:28])=[CH:24][C:23]=4[CH3:31])=[N:20][C:7]2=3)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

4

Reactant 3

HCID 27375314-Amino-1-methylpiperidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 580150324-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methyl-benzoic acid

Product 1

HCID 252535284-(9-Cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methyl-N-(1-methylpiperidin-4-yl)benzamide

Procedure

The title compound was synthesized from 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methylbenzoic acid as described in the General procedure for amide bond synthesis using HATU and 1-methylpiperidin-4-amine. The final compound was purified by reverse phase HPLC and basified to give the free base 1H NMR (400 MHz, DMSO-d6) δ ppm 1.42-2.04 (m, 16 H) 2.10-2.22 (m, 3 H) 2.29 (s, 3 H) 2.77 (d, J=11.1 Hz, 2 H) 3.72 (dd, J=7.3, 4.0 Hz, 1 H) 3.98 (t, J=14.0 Hz, 2 H) 4.60 (t, J=8.2 Hz, 1 H) 7.64 (d, J=8.3 Hz, 1 H) 7.68-7.80 (m, 2 H) 8.08 (d, J=7.8 Hz, 1 H) 8.19 (s, 1 H) 8.60 (s, 1 H). [M+H] calc'd for C27H35F2N7O2, 528; found 528.

Workup

  1. customas described in the General procedure for amide bond synthesis
  2. customThe final compound was purified by reverse phase HPLC
  3. customto give the free base 1H NMR (400 MHz, DMSO-d6) δ ppm 1.42-2.04 (m, 16 H) 2.10-2.22 (m, 3 H) 2.29 (s, 3 H) 2.77 (d, J=11.1 Hz, 2 H) 3.72 (dd, J=7.3, 4.0 Hz, 1 H) 3.98 (t, J=14.0 Hz, 2 H) 4.60 (t, J=8.2 Hz, 1 H) 7.64 (d, J=8.3 Hz, 1 H) 7.68-7.80 (m, 2 H) 8.08 (d, J=7.8 Hz, 1 H) 8.19 (s, 1 H) 8.60 (s, 1 H)

Sources & evidence

ORD record
ord-8c8bf40debe4446eb957f8d61983fe54
Source dataset
uspto-grants-2012_11
Patent number
US08318727B2

Reaction notes

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