Methanol → HCID 57955592, compound

HRID 1881009Notes

Reaction equation

HRID 1881009 reaction equation
[NH:1]1[CH2:4][CH:3]([NH:5][C:6](=[O:37])[C:7]2[CH:12]=[C:11]([O:13][CH3:14])[C:10]([NH:15][C:16]3[N:17]=[CH:18][C:19]4[N:25]([CH3:26])[C:24](=[O:27])[C:23]([F:29])([F:28])[CH2:22][N:21]([CH:30]5[CH2:34][CH2:33][CH2:32][CH2:31]5)[C:20]=4[N:35]=3)=[CH:9][C:8]=2[F:36])[CH2:2]1.C(Cl)Cl.CO.[C:43]1(=O)[CH2:47][CH2:46][CH2:45][CH2:44]1>CC(O)=O>[CH:30]1([N:21]2[CH2:22][C:23]([F:28])([F:29])[C:24](=[O:27])[N:25]([CH3:26])[C:19]3[CH:18]=[N:17][C:16]([NH:15][C:10]4[C:11]([O:13][CH3:14])=[CH:12][C:7]([C:6]([NH:5][CH:3]5[CH2:2][N:1]([CH:43]6[CH2:47][CH2:46][CH2:45][CH2:44]6)[CH2:4]5)=[O:37])=[C:8]([F:36])[CH:9]=4)=[N:35][C:20]2=3)[CH2:34][CH2:33][CH2:32][CH2:31]1

Participants

6

Reactant 4

HCID 887MethanolHCID 6344DichloromethaneHCID 8452CyclopentanoneHCID 57955666HCID 57955666, compound

Product 1

HCID 57955592HCID 57955592, compoundYield 9%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution of N-(azetidin-3-yl)-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)-2-fluoro-5-methoxybenzamide (100 mg, 0.19 mmol) in AcOH:DCM:MeOH (2.5 mL, 1:2:2) was added cyclopentanone (100 μL, 1.09 mmol), borane-pyridine complex (100 μL, 0.8 mmol), and left to stir for 3 h. The solvent was then removed and the product purified by reverse phase HPLC, free based, and lyophilized to yield a white solid (5.0 mg, 9%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.23-1.35 (m, 2 H) 1.38-1.78 (m, 11 H) 1.96 (br. s., 2 H) 2.67 (br. s., 1 H) 2.87 (t, J=7.33 Hz, 2 H) 3.49 (t, J=7.33 Hz, 2 H) 3.91 (s, 3 H) 4.08 (t, J=13.77 Hz, 2 H) 4.33-4.44 (m, 1 H) 4.78-4.88 (m, 1 H) 7.19 (d, J=6.57 Hz, 1 H) 8.05 (s, 1 H) 8.25 (d, J=13.39 Hz, 1 H) 8.30 (s, 1 H) 8.41 (dd, J=6.82, 3.03 Hz, 1 H). [M+H] calc'd for C29H36F3N7O3, 588; found 588.

Workup

  1. waitleft
  2. customThe solvent was then removed
  3. customthe product purified by reverse phase HPLC

Sources & evidence

ORD record
ord-b63c0e479b4740049d07c096e18c080c
Source dataset
uspto-grants-2012_11
Patent number
US08318727B2

Reaction notes

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