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-ethyl-N-(1-methylpiperidin-4-yl)benzamide

HRID 1880851Notes

Reaction equation

HRID 1880851 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[CH2:31][CH3:32])=[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.[CH3:57][N:58]1[CH2:63][CH2:62][CH:61]([NH2:64])[CH2:60][CH2:59]1>>[CH:1]1([N:6]2[CH2:12][C:11]([F:13])([F:14])[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:64][CH:61]5[CH2:62][CH2:63][N:58]([CH3:57])[CH2:59][CH2:60]5)=[O:28])=[CH:24][C:23]=4[CH2:31][CH3:32])=[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 580150654-(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-ethylbenzoic acid

Product 1

HCID 252535294-(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-ethyl-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-ethylbenzoic 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 1.14 (t, J=8.0 Hz, 3 H) 1.23-1.69 (m, 11 H) 1.77 (m, 4 H) 1.99 (m, 2 H) 2.20 (s, 3 H) 2.69 (q, J=7.3 Hz, 2 H) 3.75 (s, 1 H) 3.97 (t, J=14.2 Hz, 2 H) 4.54 (t, J=8.1 Hz, 1 H) 7.57-7.81 (m, 3 H) 8.12 (d, J=7.8 Hz, 1 H) 8.17 (s, 1 H) 8.61 (s, 1 H). [M+H] calc'd for C28H37F2N7O2, 542; found 542.

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 1.14 (t, J=8.0 Hz, 3 H) 1.23-1.69 (m, 11 H) 1.77 (m, 4 H) 1.99 (m, 2 H) 2.20 (s, 3 H) 2.69 (q, J=7.3 Hz, 2 H) 3.75 (s, 1 H) 3.97 (t, J=14.2 Hz, 2 H) 4.54 (t, J=8.1 Hz, 1 H) 7.57-7.81 (m, 3 H) 8.12 (d, J=7.8 Hz, 1 H) 8.17 (s, 1 H) 8.61 (s, 1 H)

Sources & evidence

ORD record
ord-537c68a3785b4574914aa6815b6cca84
Source dataset
uspto-grants-2012_11
Patent number
US08318727B2

Reaction notes

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