Chlorotrimethylsilane → HCID 123494783, compound

HRID 1429749Notes

Reaction equation

HRID 1429749 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](=[O:35])[CH2:32][C:33]#[N:34])[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.[CH3:36][C:37]([N:41]1[CH2:44][C:43]2([CH2:47][O:46][CH2:45]2)[CH2:42]1)([CH3:40])[CH:38]=O.N1CCCC1.Cl[Si](C)(C)C>C(Cl)Cl.C([O-])(O)=O.[Na+]>[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:32](=[CH:38][C:37]([CH3:40])([N:41]4[CH2:42][C:43]5([CH2:47][O:46][CH2:45]5)[CH2:44]4)[CH3:36])[C:33]#[N:34])=[O:35])[CH2:26]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)=[CH:13][C:12]=3[F:24])[C:3]=12

Participants

7

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 31268PyrrolidineHCID 867144983-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]-3-oxopropanenitrileHCID 90001220HCID 90001220, compound

Product 1

HCID 123494783HCID 123494783, compoundYield 46.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a mixture of (R)-3-(3-(4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)-3-oxopropanenitrile (222 mg, 0.46 mmol), 2-methyl-2-(6-oxa-2-azaspiro[3.3]heptan-2-yl)propanal (231.17 mg, 1.37 mmol) and pyrrolidine (0.23 mL, 2.73 mmol) in DCM (10 mL) at room temperature was added chloro(trimethyl)silane (0.17 mL, 1.37 mmol). After stirring 2 h, the solution was diluted with sat. NaHCO3 and extracted with DCM. The organic layers were combined, dried (MgSO4), filtered and concentrated. The crude material was purified by chromatography to obtain 133 mg of 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-(6-oxa-2-azaspiro[3.3]heptan-2-yl)pent-2-enenitrile. MS (pos. ion) m/z: 623 (M+1).

Workup

  1. extractionextracted with DCM
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude material was purified by chromatography

Sources & evidence

ORD record
ord-383e80296c4147f695fbbcc5135731e4
Source dataset
uspto-grants-2015_01
Patent number
US08940744B2

Reaction notes

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