Piperidine → HCID 123730062, compound

HRID 1854964Notes

Reaction equation

HRID 1854964 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:25][C@@H:26]3[CH2:30][C:29]([F:32])([F:31])[CH2:28][N:27]3[C:33](=[O:37])[CH2:34][C:35]#[N:36])[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:13][C:12]=3[F:24])[C:3]=12.[CH:38]1([CH:41]=O)[CH2:40][CH2:39]1.N1CCCCC1>C(O)C>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:25][C@@H:26]3[CH2:30][C:29]([F:31])([F:32])[CH2:28][N:27]3[C:33]([C:34](=[CH:41][CH:38]3[CH2:40][CH2:39]3)[C:35]#[N:36])=[O:37])[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:13][C:12]=3[F:24])[C:3]=12

Participants

5

Reactant 3

HCID 8082PiperidineHCID 123114CyclopropanecarboxaldehydeHCID 86714511HCID 86714511, compound

Product 1

HCID 123730062HCID 123730062, compoundYield 18%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 3-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-4,4-difluoropyrrolidin-1-yl]-3-oxopropanenitrile (120 mg, 0.24 mmol, 1.00 equiv), cyclopropanecarbaldehyde (80 mg, 1.14 mmol, 5.00 equiv), piperidine (41 mg, 0.48 mmol, 2.00 equiv) in ethanol (10 mL) was stirred at 70° C. for 2 h. The resulting mixture was concentrated under vacuum. The residue was purified on Prep-HPLC. Conditions: (1#-Pre-HPLC-001(SHIMADZU)): Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, water with 0.05% TFA and CH3CN (40% CH3CN up to 100% in 20 min); Detector, 254 nm, to give 24 mg (18%) of the title compound as a white solid. LC-MS m/z: 560 (M+1). H-NMR (400 MHz, CDCl3, ppm): 11.94 (brs, 1H) 8.29 (s, 1H), 7.55-7.45 (m, 3H), 7.31-7.24 (m, 1H), 7.14 (d, J=7.6 Hz, 2H), 7.00 (dd, J=8.8, 2.4 Hz, 1H), 6.90-6.87 (m, 1H), 6.07 (brs, 1H), 4.97-5.05 (m, 1H), 4.70-4.67 (m, 1H), 3.94-3.77 (m, 2H), 2.10 (s, 1H), 1.45-1.36 (m, 2H), 1.27-1.14 (m, 2H).

Workup

  1. concentrationThe resulting mixture was concentrated under vacuum
  2. customThe residue was purified on Prep-HPLC

Sources & evidence

ORD record
ord-0c2929a7c56249cb800c6bee6941218d
Source dataset
uspto-grants-2015_02
Patent number
US08962831B2

Reaction notes

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