Acetic Acid → HCID 57955543, compound

HRID 1881013Notes

Reaction equation

HRID 1881013 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:40]=[CH:39][C:25]([C:26]([NH:28][CH:29]5[CH2:32][N:31]([CH:33]6[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]6)[CH2:30]5)=[O:27])=[CH:24][C:23]=4[O:41][CH3:42])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.CC(O)=O.[CH:47]1([CH:50]=O)[CH2:49][CH2:48]1>CO>[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:40]=[CH:39][C:25]([C:26]([NH:28][CH:29]5[CH2:30][N:31]([CH:33]6[CH2:38][CH2:37][N:36]([CH2:50][CH:47]7[CH2:49][CH2:48]7)[CH2:35][CH2:34]6)[CH2:32]5)=[O:27])=[CH:24][C:23]=4[O:41][CH3:42])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 123114CyclopropanecarboxaldehydeHCID 57955617HCID 57955617, compound

Product 1

HCID 57955543HCID 57955543, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 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-methoxy-N-(1-(piperidin-4-yl)azetidin-3-yl)benzamide (13 mg, 0.023 mmol) in MeOH (2.5 mL) was added AcOH (0.03 mL), cyclopropane aldehyde (3 μL, 0.034 mmol), borane-pyridine complex (10 μL, 0.08 mmol), and left to stir overnight. The solvent was then removed and the product purified by reverse phase HPLC, free based, and lyophilized to yield a white solid (6.4 mg, 44%). 1H NMR (400 MHz, DMSO-d6) δ ppm −0.03-0.14 (m, 3 H) 0.34-0.51 (m, 2 H) 0.80 (s, 1 H) 1.17 (d, J=2.53 Hz, 2 H) 1.60 (br. s., 6 H) 1.71 (br. s., 2 H) 1.94 (br. s., 5 H) 2.13 (d, J=6.32 Hz, 2 H) 2.82 (br. s., 2 H) 2.96 (t, J=7.20 Hz, 2 H) 3.52 (t, J=7.20 Hz, 2 H) 3.92 (s, 1 H) 4.05 (t, J=14.02 Hz, 2 H) 4.38-4.50 (m, 1 H) 4.70-4.82 (m, 1 H) 7.41-7.58 (m, 2 H) 7.98 (s, 1 H) 8.22-8.33 (m, 2 H) 8.61 (d, J=6.57 Hz, 1 H). [M+H] calc'd for C33H44F2N8O3, 638; found 638.

Workup

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

Sources & evidence

ORD record
ord-5d5f923a36a542c9a86682f21f8323a8
Source dataset
uspto-grants-2012_11
Patent number
US08318727B2

Reaction notes

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