Tetrabutylammonium Fluoride → HCID 90003318, compound

HRID 1778428Notes

Reaction equation

HRID 1778428 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@@H:25]3[CH2:30][CH2:29][CH2:28][N:27]([C:31]([C:33](=[CH:36][C:37]([N:40]4[CH2:43][CH:42]([O:44][Si](C(C)(C)C)(C5C=CC=CC=5)C5C=CC=CC=5)[CH2:41]4)([CH3:39])[CH3:38])[C:34]#[N:35])=[O:32])[CH2:26]3)[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.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@@H:25]3[CH2:30][CH2:29][CH2:28][N:27]([C:31]([C:33](=[CH:36][C:37]([N:40]4[CH2:43][CH:42]([OH:44])[CH2:41]4)([CH3:39])[CH3:38])[C:34]#[N:35])=[O:32])[CH2:26]3)[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

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 90003203HCID 90003203, compound

Product 1

HCID 90003318HCID 90003318, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-((R)-3-(4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carbonyl)-4-(3-(tert-butyldiphenylsilyloxy)azetidin-1-yl)-4-methylpent-2-enenitrile (300 mg, 0.36 mmol, 1.0 equiv) in THF (8 mL) was added a solution of 1 M TBAF in THF (0.432 mL, 0.432 mmoL). The resulting mixture was stirred at rt overnight. The mixture was concentrated and the crude product was purified by prep-HPLC eluting with CH3CN/H2O (0.05% TFA). The organic phase was removed under reduced pressure and the resulting aqueous solution was diluted with sat.Na2CO3 solution and extracted with DCM. The combined organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. This resulted in 18.1 mg of 2-((R)-3-(4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carbonyl)-4-(3-hydroxyazetidin-1-yl)-4-methylpent-2-enenitrile as a white solid. LCMS (ESI, pos. ion) m/z: 597 (M+1).

Workup

  1. concentrationThe mixture was concentrated
  2. customthe crude product was purified
  3. washby prep-HPLC eluting with CH3CN/H2O (0.05% TFA)
  4. customThe organic phase was removed under reduced pressure
  5. additionthe resulting aqueous solution was diluted
  6. extractionNa2CO3 solution and extracted with DCM
  7. washThe combined organic layer was washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under vacuum
  11. customThis resulted in 18.1 mg of 2-((R)-3-(4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carbonyl)-4-(3-hydroxyazetidin-1-yl)-4-methylpent-2-enenitrile as a white solid

Sources & evidence

ORD record
ord-54e67532d21f4c609e7479db86e6a928
Source dataset
uspto-grants-2016_02
Patent number
US09266895B2

Reaction notes

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