Sodium Hydroxide → HCID 68639188, compound

HRID 639999Notes

Reaction equation

HRID 639999 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].FC(F)(F)C(O)=O.FC(F)(F)C(O)=O.[F:29][C:30]1[CH:31]=[C:32]([NH:36][C:37](=[O:62])[CH2:38][N:39]2[CH:43]=[C:42]([NH:44][C:45]3[C:54]4[C:49](=[CH:50][C:51]([O:55][CH2:56][C@@H:57]5[CH2:61][CH2:60][CH2:59][NH:58]5)=[CH:52][CH:53]=4)[N:48]=[CH:47][N:46]=3)[CH:41]=[N:40]2)[CH:33]=[CH:34][CH:35]=1.[Si:63]([O:70][CH2:71][CH:72]=O)([C:66]([CH3:69])([CH3:68])[CH3:67])([CH3:65])[CH3:64].[OH-].[Na+]>O1CCCC1.CO.C(O)(=O)C>[Si:63]([O:70][CH2:71][CH2:72][N:58]1[CH2:59][CH2:60][CH2:61][C@H:57]1[CH2:56][O:55][C:51]1[CH:50]=[C:49]2[C:54]([C:45]([NH:44][C:42]3[CH:41]=[N:40][N:39]([CH2:38][C:37]([NH:36][C:32]4[CH:33]=[CH:34][CH:35]=[C:30]([F:29])[CH:31]=4)=[O:62])[CH:43]=3)=[N:46][CH:47]=[N:48]2)=[CH:53][CH:52]=1)([C:66]([CH3:69])([CH3:68])[CH3:67])([CH3:65])[CH3:64]

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 41877882-((Tert-butyldimethylsilyl)oxy)acetaldehydeHCID 5049666Sodium triacetoxyborohydride3×HCID 86609384HCID 86609384, compound

Product 1

HCID 68639188HCID 68639188, compoundYield 31%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Sodium triacetoxyborohydride (0.11 g, 0.52 mmol) was added to a mixture of N-(3-fluorophenyl)-2-[4-({7-[(2S)-pyrrolidin-2-ylmethoxy]quinazolin-4-yl}amino)-1H-pyrazol-1-yl]acetamide bis(trifluoroacetate) (0.20 g, 0.29 mmol) and (tert-butyldimethylsilyloxy)acetaldehyde (0.10 ml, 0.52 mmol) in tetrahydrofuran (9 ml) and methanol (3 ml) containing a catalytic amount of acetic acid. The mixture was stirred at room temperature for 1 hour. A further portion of sodium triacetoxyborohydride (0.22 g, 1.04 mmol) was added and the mixture stirred at room temperature for 1 hour. A further portion of sodium triacetoxyborohydride (0.22 g, 1.04 mmol) was added and the mixture stirred at room temperature overnight. The mixture was poured into sodium hydroxide solution (1M, 50 ml) and extracted with dichloromethane. The organic layer was separated, washed with brine, dried over magnesium sulphate and then evaporated to leave a yellow film which was purified by silica gel chromatography. Elution with 5 to 10% methanol in dichloromethane gave 2-{4-[(7-{[(2S)-1-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)pyrrolidin-2-yl]methoxy}quinazolin-4-yl)amino]-1H-pyrazol-1-yl}-N-(3-fluorophenyl)acetamide (0.055 g, 31% yield): MS (+ve ESI): 620 (M+H)+.

Workup

  1. stirringthe mixture stirred at room temperature for 1 hour
  2. stirringthe mixture stirred at room temperature overnight
  3. extractionextracted with dichloromethane
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried over magnesium sulphate
  7. customevaporated
  8. customto leave a yellow film which
  9. customwas purified by silica gel chromatography
  10. washElution with 5 to 10% methanol in dichloromethane

Sources & evidence

ORD record
ord-48b1d59d1f314d34a0ed8c47440c553f
Source dataset
uspto-grants-2010_04
Patent number
US07691867B2

Reaction notes

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