Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → N-(1-acetylazetidin-3-yl)-4-(9-cyclohexyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxybenzamide

HRID 914123Notes

Reaction equation

HRID 914123 reaction equation
[CH:1]1([N:7]2[CH2:13][C:12]([F:15])([F:14])[C:11](=[O:16])[N:10]([CH3:17])[C:9]3[CH:18]=[N:19][C:20]([NH:22][C:23]4[CH:31]=[CH:30][C:26]([C:27]([OH:29])=O)=[CH:25][C:24]=4[O:32][CH3:33])=[N:21][C:8]2=3)[CH2:6][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.[NH2:58][CH:59]1[CH2:62][N:61]([C:63](=[O:65])[CH3:64])[CH2:60]1>>[C:63]([N:61]1[CH2:62][CH:59]([NH:58][C:27](=[O:29])[C:26]2[CH:30]=[CH:31][C:23]([NH:22][C:20]3[N:19]=[CH:18][C:9]4[N:10]([CH3:17])[C:11](=[O:16])[C:12]([F:14])([F:15])[CH2:13][N:7]([CH:1]5[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]5)[C:8]=4[N:21]=3)=[C:24]([O:32][CH3:33])[CH:25]=2)[CH2:60]1)(=[O:65])[CH3:64]

Participants

4

Reactant 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 252536804-(9-cyclohexyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acidHCID 545278501-(3-Aminoazetidin-1-yl)ethan-1-one

Product 1

HCID 25254620N-(1-acetylazetidin-3-yl)-4-(9-cyclohexyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxybenzamide

Procedure

The title compound was synthesized from 4-(9-cyclohexyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acid as described in the General procedure for amide bond synthesis using HATU and 1-(3-aminoazetidin-1-yl)ethanone. The final compound was purified by reverse phase HPLC and basified to give the free base. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.20 (t, J=12.4 Hz, 1H) 1.34-1.45 (bq, 2H) 1.57-1.68 (m, 3H) 1.78 (s, 3H) 1.84 (m, 3H) 3.32 (s, 3H) 3.88 (m, 1H) 3.95 (s, 3H) 4.03-4.12 (m, 4H) 4.42 (t, J=8.2 Hz, 1H) 4.45-4.51 (m, 1H) 4.68 (q, J=6.8 Hz, 3H) 7.51 (dd, J=8.3, 1.8 Hz, 1H) 7.54 (d, J=1.5 Hz, 1H) 7.93 (s, 1H) 8.22 (s, 1H) 8.30 (d, J=8.3 Hz, 1H) 8.89 (d, J=6.8 Hz, 1H). [M+H] calc'd for C27H33F2N7O4 558. found 558.

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

Sources & evidence

ORD record
ord-d5a9573625f04cd6b5e65fd04e50720d
Source dataset
uspto-grants-2011_09
Patent number
US08026234B2

Reaction notes

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