Piperidine → HCID 71015594, compound

HRID 1854890Notes

Reaction equation

HRID 1854890 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@@H:30]3[CH2:35][CH2:34][CH2:33][N:32]([C:36](=[O:40])[CH2:37][C:38]#[N:39])[CH2:31]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:29])[C:19]4[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=4)=[CH:13][CH:12]=3)[C:3]=12.[CH:41]1([CH:44]=O)[CH2:43][CH2:42]1.N1CCCCC1>CO>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@@H:30]3[CH2:35][CH2:34][CH2:33][N:32]([C:36](=[O:40])[C:37]([C:38]#[N:39])=[CH:44][CH:41]4[CH2:43][CH2:42]4)[CH2:31]3)[N:9]=[C:10]([C:11]3[CH:12]=[CH:13][C:14]([NH:17][C:18](=[O:29])[C:19]4[CH:20]=[CH:21][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:23][CH:24]=4)=[CH:15][CH:16]=3)[C:3]=12

Participants

5

Reactant 3

HCID 8082PiperidineHCID 123114CyclopropanecarboxaldehydeHCID 86714461HCID 86714461, compound

Product 1

HCID 71015594HCID 71015594, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

Into a 10-mL round-bottom flask, was placed (R)—N-(4-[4-amino-1-[1-(2-cyanoacetyl)piperidin-3-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl]phenyl)-4-(trifluoromethyl)-benzamide (65 mg, 0.12 mmol, 1.00 equiv), cyclopropanecarbaldehyde (16.6 mg, 0.24 mmol, 2.00 equiv), piperidine (10 mg, 0.12 mmol, 0.99 equiv), methanol (5 mL). The resulting solution was stirred for 12 h at 25° C. The resulting mixture was concentrated under vacuum and the residue was loaded onto a silica gel column and eluted with dichloromethane/methanol (50:1) to give 43 mg (60%) of (R)—N-[4-(4-amino-1-[1-[2-cyano-2-(cyclopropylmethylidene)acetyl]piperidin-3-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl)phenyl]-4-(trifluoromethyl)benzamide as a white solid. MS (ESI, pos. ion) m/z: 601 (M+1), 1HNMR (300 MHz, CDCl3, ppm), 8.6 (1H, s), 8.348 (1H, s), 8.065˜8.038 (2H, d, J=8.1),7.880˜7.852 (1H, d, J=8.4), 7.768˜7.659 (4H, m), 6.532˜6.496 (1H, dJ=10.8), 5.949 (2H, s), 4.976˜4.907 (1H, m), 4.638˜3.218 (4H, m), 2.436˜1.818 (5H, m), 1.221˜1.198 (2H, m),0.89˜0.772 (2H, m).

Workup

  1. customInto a 10-mL round-bottom flask, was placed
  2. concentrationThe resulting mixture was concentrated under vacuum
  3. washeluted with dichloromethane/methanol (50:1)

Sources & evidence

ORD record
ord-8d29a799ad7e4751be444488386f8d15
Source dataset
uspto-grants-2015_02
Patent number
US08962831B2

Reaction notes

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