Acetic Acid → 1207830-66-7

HRID 1098064Notes

Reaction equation

HRID 1098064 reaction equation
CCCC[N+](CCCC)(CCCC)CCCC.[F-].[Cl:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([C:26]#[N:27])[C:21]=1[N:28]1[C:32]2=[N:33][CH:34]=[N:35][C:36]([O:37][C@@H:38]([CH2:49][O:50][C@H:51]([CH3:64])[CH2:52][O:53][Si](C(C)C)(C(C)C)C(C)C)[C:39]([NH:41][C:42]3[CH:47]=[N:46][C:45]([CH3:48])=[CH:44][N:43]=3)=[O:40])=[C:31]2[CH:30]=[N:29]1.C(O)(=O)C>C1COCC1>[Cl:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([C:26]#[N:27])[C:21]=1[N:28]1[C:32]2[N:33]=[CH:34][N:35]=[C:36]([O:37][C@@H:38]([CH2:49][O:50][C@H:51]([CH3:64])[CH2:52][OH:53])[C:39]([NH:41][C:42]3[CH:47]=[N:46][C:45]([CH3:48])=[CH:44][N:43]=3)=[O:40])[C:31]=2[CH:30]=[N:29]1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 2724141Tetrabutylammonium FluorideHCID 46938169HCID 46938169, compound

Product 1

HCID 461756111207830-66-7Yield 85.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
22 °C

Procedure

1M TBAF in THF (5.11 mL, 5.11 mmol) was added to (2S)-2-(1-(2-chloro-6-cyanophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-methylpyrazin-2-yl)-3-((R)-1-(triisopropylsilyloxy)propan-2-yloxy)propanamide (Intermediate AZ1) (3.4 g, 5.11 mmol) and acetic acid (0.307 g, 5.11 mmol) in THF (35 mL). The resulting solution was stirred at 22° C. for 20 hours. It was quenched with NH4Cl solution (sat., 25 mL) and diluted with EtOAc (50 mL). The organic phase was washed with saturated sodium bicarbonate (25 mL), water (20 mL), brine (20 mL), dried (MgSO4) and evaporated. The crude product was purified by flash silica chromatography, eluting with EtOAc to afford the product (2.23 g, 85%). This was crystallised from EtOAc (10 mL) and iso-hexane (6 mL) to give the desired product as a white crystalline powder (1.9 g, 73%) confirmed to be of the same crystalline form as that described previously.

Workup

  1. customIt was quenched with NH4Cl solution (sat., 25 mL)
  2. additiondiluted with EtOAc (50 mL)
  3. washThe organic phase was washed with saturated sodium bicarbonate (25 mL), water (20 mL), brine (20 mL)
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customThe crude product was purified by flash silica chromatography
  7. washeluting with EtOAc

Sources & evidence

ORD record
ord-251ce15b4f5b46e28d96471dce28fb07
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

Loading…