Dimethylformamide → HCID 86611044, compound

HRID 1821595Notes

Reaction equation

HRID 1821595 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:16]2[C:11](=[N:12][C:13]([O:22][C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=3[F:30])=[N:14][C:15]=2[NH:17][CH2:18][C@@H:19]([OH:21])[CH3:20])[N:10](OCCC[Si](C)(C)C)[N:9]=1.[C:39]([NH:46][C@H:47]([C:51]([OH:53])=O)[CH:48]([CH3:50])[CH3:49])([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40].[CH3:54]N(C=O)C>CN(C)C1C=CN=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:16]2[C:11](=[N:12][C:13]([O:22][C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=3[F:30])=[N:14][C:15]=2[NH:17][CH2:18][C@@H:19]([O:21][C:51](=[O:53])[C@@H:47]([NH:46][C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH:48]([CH3:50])[CH3:49])[CH3:20])[N:10]([CH3:54])[N:9]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 83693Boc-L-ValineHCID 69059790HCID 69059790, compound

Product 1

HCID 86611044HCID 86611044, compound

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Conditions

Temperature
120 °C

Procedure

A solution of (S)-1-[3-(2-Chloro-phenyl)-6-(2,4-difluoro-phenoxy)-1-(3-trimethylsilanyl-propoxy)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-propan-2-ol (50 mg, 0.2846 mmol), Boc-(L)-Valine (68 mg, 0.313 mmol), 4-dimethylaminopyridine (7 mg, 0.057 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarodiimide (60 mg, 0.313 mmol) in 4 mL DMF was stirred at room temperature for three days, then heated to 120° C. for four hours. The reaction mixture was cooled and partitioned between water and ethyl acetate. The organic layer was separate, washed with 0.5N aqueous HCl, saturated aqueous sodium bicarbonate and brine, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was chromatographed on silica (0% to 50% EtOAc in hexanes) to give 50 mg of (S)-2-tert-butoxycarbonylamino-3-methyl-butyric acid (S)-2-[3-(2-chloro-phenyl)-6-(2,4-difluoro-phenoxy)-1-methyl1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-1-methyl-ethyl ester

Workup

  1. temperatureThe reaction mixture was cooled
  2. custompartitioned between water and ethyl acetate
  3. customThe organic layer was separate
  4. washwashed with 0.5N aqueous HCl, saturated aqueous sodium bicarbonate and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was chromatographed on silica (0% to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-95c94544d8f840d887c001306bf4e102
Source dataset
uspto-grants-2009_10
Patent number
US07608603B2

Reaction notes

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