Hydrochloric Acid → HCID 123421165, compound

HRID 1778431Notes

Reaction equation

HRID 1778431 reaction equation
Cl.O1CCOCC1.[NH2:8][C:9]1[N:14]=[CH:13][N:12]=[C:11]2[N:15]([CH2:32][C@@H:33]3[CH2:37][CH2:36][CH2:35][N:34]3[C:38](=[O:59])[C:39]([C:57]#[N:58])=[CH:40][C:41]([N:44]3[CH2:49][CH2:48][N:47](C(OC(C)(C)C)=O)[CH2:46][CH2:45]3)([CH3:43])[CH3:42])[N:16]=[C:17]([C:18]3[CH:23]=[CH:22][C:21]([O:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[CH:20][C:19]=3[F:31])[C:10]=12>C1COCC1>[NH2:8][C:9]1[N:14]=[CH:13][N:12]=[C:11]2[N:15]([CH2:32][C@@H:33]3[CH2:37][CH2:36][CH2:35][N:34]3[C:38]([C:39](=[CH:40][C:41]([CH3:43])([N:44]3[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]3)[CH3:42])[C:57]#[N:58])=[O:59])[N:16]=[C:17]([C:18]3[CH:23]=[CH:22][C:21]([O:24][C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=4)=[CH:20][C:19]=3[F:31])[C:10]=12

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 131732371HCID 131732371, compound

Product 1

HCID 123421165HCID 123421165, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4N HCl in dioxane (0.5 mL, 0.050 mmol) in THF (1 mL) in the ice bath, was added tert-butyl 4-[4-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidin-1-yl]-3-cyano-1,1-dimethyl-4-oxo-but-2-enyl]piperazine-1-carboxylate (32.9 mg, 0.050 mmol). The ice bath was removed, the reaction mixture was stirred for 4 h at room temperature at which point TLC and LC-MS showed the reaction was finished. The mixture was concentrated in vacuo, adjusted with NaHCO3 to pH 6-7, and the aq. layer extracted with CH2Cl2. The combined organic layer was washed by brine, dried over Na2SO4, filtered, and the solvent removed to get product 2-[(2S)-2-[[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-pyrrolidine-1-carbonyl]-4-methyl-4-piperazin-1-yl-pent-2-enenitrile (24 mg, 0.039 mmol, 85% yield) as an off white powder. LC-MS (ES, m/z): 610 [M+H]

Workup

  1. customThe ice bath was removed
  2. concentrationThe mixture was concentrated in vacuo
  3. extractionthe aq. layer extracted with CH2Cl2
  4. washThe combined organic layer was washed by brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customthe solvent removed

Sources & evidence

ORD record
ord-8b1abb5633314fe388d39d44480efeef
Source dataset
uspto-grants-2016_02
Patent number
US09266895B2

Reaction notes

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