Ammonium Chloride → HCID 57504399, compound

HRID 1098025Notes

Reaction equation

HRID 1098025 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Si]([O:36][CH2:37][CH2:38][O:39][CH2:40][C@H:41]([O:53][C:54]1[N:59]=[CH:58][N:57]=[C:56]2[N:60]([C:63]3[CH:68]=[CH:67][CH:66]=[C:65]([F:69])[C:64]=3[CH3:70])[N:61]=[CH:62][C:55]=12)[C:42]([NH:44][C:45]1[CH:50]=[CH:49][C:48]([C:51]#[N:52])=[CH:47][N:46]=1)=[O:43])(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.[Cl-].[NH4+]>C1COCC1.CCOC(C)=O>[C:51]([C:48]1[CH:49]=[CH:50][C:45]([NH:44][C:42](=[O:43])[C@@H:41]([O:53][C:54]2[C:55]3[CH:62]=[N:61][N:60]([C:63]4[CH:68]=[CH:67][CH:66]=[C:65]([F:69])[C:64]=4[CH3:70])[C:56]=3[N:57]=[CH:58][N:59]=2)[CH2:40][O:39][CH2:38][CH2:37][OH:36])=[N:46][CH:47]=1)#[N:52]

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 2724141Tetrabutylammonium FluorideHCID 57504522HCID 57504522, compound

Product 1

HCID 57504399HCID 57504399, compoundYield 72%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of tetrabutylammonium fluoride (1M in THF, 1.504 mL, 1.50 mmol) was added dropwise to a stirred solution of (2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-N-(5-cyanopyridin-2-yl)-2-(1-(3-fluoro-2-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanamide (Intermediate AF1) (520 mg, 0.73 mmol) in THF (15 mL) over a period of 1 minute and the resulting solution stirred at ambient temperature for 3 hours. Saturated ammonium chloride (20 mL) was added to the reaction mixture which was then diluted with EtOAc (25 mL), and washed sequentially with water (25 mL) and saturated brine (25 mL). The organic layer was dried (MgSO4), filtered and evaporated in vacuo. The crude product was purified by flash silica chromatography, elution gradient 60 to 100% EtOAc in isohexane and then by chiral HPLC to afford the product (250 mg, 72%).

Workup

  1. washwashed sequentially with water (25 mL) and saturated brine (25 mL)
  2. dry with materialThe organic layer was dried (MgSO4)
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. customThe crude product was purified by flash silica chromatography, elution gradient 60 to 100% EtOAc in isohexane

Sources & evidence

ORD record
ord-462d672390244f41b664e9848e855bb8
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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