Isobutyraldehyde → HCID 86714561, compound

HRID 409184Notes

Reaction equation

HRID 409184 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:25][C@@H:26]([NH:28][C:29](=[O:33])[CH2:30][C:31]#[N:32])[CH3:27])[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.[CH3:34][CH:35]([CH3:38])[CH:36]=O.N1CCCCC1>CO>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:25][C@@H:26]([NH:28][C:29](=[O:33])[C:30]([C:31]#[N:32])=[CH:34][CH:35]([CH3:38])[CH3:36])[CH3:27])[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)=[CH:13][C:12]=3[F:24])[C:3]=12

Participants

5

Reactant 3

HCID 6561IsobutyraldehydeHCID 8082PiperidineHCID 71015234HCID 71015234, compound

Product 1

HCID 86714561HCID 86714561, compoundYield 17%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A suspension of N-[(2S)-1-[4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]propan-2-yl]-2-cyanoacetamide (250 mg, 0.56 mmol, 1.00 equiv), 2-methylpropanal (81 mg, 1.12 mmol, 2.00 equiv) and piperidine (47 mg, 0.55 mmol, 1.00 equiv) in methanol (15 mL) was stirred at room temperature overnight. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1/1). The purified product was re-purified on Prep-HPLC eluting with TFA (0.05%)/H2O and CH3CN. The organic phase was removed off under reduced pressure. The aqueous phase was adjusted to 10 with potassium carbonate, which was extracted with DCM. The organic layers were combined, washed with brine, dried over sodium sulfated, filtrated and concentrated. This resulted in 46.4 mg (17%) of the title compound as a white solid. LC-MS m/z: 500 (M+1). 1H-NMR (400 MHz, CDCl3, ppm): 8.49 (s, 1H), 8.12 (d, J=7.2 Hz, 1H), 7.60 (t, J=8.8 Hz, 1H), 7.44 (m, 3H), 7.25-7.21 (m, 1H), 7.13 (d, J=8.4 Hz, 2H), 6.94 (dd, J=8.4, 2.4 Hz, 1H), 6.88 (dd, J=11.2, 2.4 Hz, 1H), 5.51 (brs, 2H), 4.74-4.55 (m, 3H), 3.00-2.95 (m, 1H), 1.21 (d, J=6.8, 3H), 1.15 (d, J=6.8 Hz, 6H).

Workup

  1. concentrationThe resulting mixture was concentrated under vacuum
  2. customThe purified product was re-purified on Prep-HPLC
  3. washeluting with TFA (0.05%)/H2O and CH3CN
  4. customThe organic phase was removed off under reduced pressure
  5. extractionwas extracted with DCM
  6. washwashed with brine
  7. dry with materialdried over sodium
  8. filtrationfiltrated
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-68a1cbf588a846c0a7f83c97b5fdb0c7
Source dataset
uspto-grants-2014_06
Patent number
US08759358B1

Reaction notes

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