Piperidine → HCID 86714496, compound

HRID 1854947Notes

Reaction equation

HRID 1854947 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@@H:26]3[CH2:31][CH2:30][CH2:29][N:28]([C:32](=[O:36])[CH2:33][C:34]#[N:35])[CH2:27]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=4[F:25])=[CH:13][CH:12]=3)[C:3]=12.N1[CH2:42][CH2:41][CH2:40][CH2:39]C1.C1(C=O)CC1>CO>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@@H:26]3[CH2:31][CH2:30][CH2:29][N:28]([C:32]([C:33](=[CH:39][CH:40]4[CH2:42][CH2:41]4)[C:34]#[N:35])=[O:36])[CH2:27]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=4[F:25])=[CH:13][CH:12]=3)[C:3]=12

Participants

5

Reactant 3

HCID 8082PiperidineHCID 123114CyclopropanecarboxaldehydeHCID 71015144HCID 71015144, compound

Product 1

HCID 86714496HCID 86714496, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

Into a 10 sealed tube, was placed a solution of 3-[(3R)-3-[4-amino-3-[4-(2,5-difluorophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]-3-oxopropanenitrile (150 mg, 031 mmol, 1.00 equiv) in methanol (5 mL), piperidine (78 mg, 0.92 mmol, 3.0 equiv), and cyclopropanecarbaldehyde (64 mg, 0.91 mmol, 3.0 equiv). The resulting solution was stirred for 12 h at 25° C. and then concentrated under vacuum. The resulting solution was diluted with dichloromethane and washed with saturated aqueous ammonium chloride, water and brine. The organics were dried over anhydrous sodium sulfate and concentrated. The residue was loaded onto a silica gel column and eluted with dichloromethane/methanol (20/1) to give 38 mg (23%) of 2-[[(3R)-3-[4-amino-3-[4-(2,5-difluorophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]carbonyl]-3-cyclopropylprop-2-enenitrile as a white solid. LC-MS (ES, m/z): 542 [M+H], H-NMR (CDCl3, ppm): δ8.51 (s, 1H); δ7.66 (d, 2H); δ7.12 (m, 3H); δ6.88 (m, 2H); δ6.51 (d, 1H); δ5.57 (s, 2H); δ4.95 (m, 1H); δ4.82 (m, 1H); δ4.23 (m, 1H); δ3.65 (m, 1H); δ3.28 (m, 1H); δ2.33 (m, 2H); δ2.01 (m, 2H); δ1.83 (m, 1H); δ1.20 (m, 2H); δ0.78 (m, 2H).

Workup

  1. concentrationconcentrated under vacuum
  2. additionThe resulting solution was diluted with dichloromethane
  3. washwashed with saturated aqueous ammonium chloride, water and brine
  4. dry with materialThe organics were dried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. washeluted with dichloromethane/methanol (20/1)

Sources & evidence

ORD record
ord-81f08f882a824df4ad00984826ea5227
Source dataset
uspto-grants-2015_02
Patent number
US08962831B2

Reaction notes

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