Ammonia → (S)-4-Amino-N-(1-cyano-2-(4-(1-oxoisoindolin-5-yl)phenyl)ethyl)tetrahydro-2H-pyran-4-carboxamide

HRID 216940Notes

Reaction equation

HRID 216940 reaction equation
[C:1]([C@@H:3]([NH:21][C:22]([C:24]1([NH:30]C(=O)OC(C)(C)C)[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1)=[O:23])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[C:16](=[O:20])[NH:15][CH2:14]3)=[CH:7][CH:6]=1)#[N:2].N>C(O)=O.O>[NH2:30][C:24]1([C:22]([NH:21][C@H:3]([C:1]#[N:2])[CH2:4][C:5]2[CH:6]=[CH:7][C:8]([C:11]3[CH:12]=[C:13]4[C:17](=[CH:18][CH:19]=3)[C:16](=[O:20])[NH:15][CH2:14]4)=[CH:9][CH:10]=2)=[O:23])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1

Participants

5

Reactant 2

HCID 222AmmoniaHCID 59568570(S)-tert-Butyl 4-(1-cyano-2-(4-(1-oxoisoindolin-5-yl)phenyl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

Product 1

HCID 46944250(S)-4-Amino-N-(1-cyano-2-(4-(1-oxoisoindolin-5-yl)phenyl)ethyl)tetrahydro-2H-pyran-4-carboxamideYield 54.6%

Reagents, catalysts & solvents 2

HCID 284Formic AcidSolventHCID 962WaterSolvent

Procedure

(S)-tert-Butyl 4-(1-cyano-2-(4-(1-oxoisoindolin-5-yl)phenyl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 15, step (ii), 160 mg) was stirred in formic acid (0.5 mL) at 50° C. for 20 min. The reaction mixture was cooled to room temperature and the mixture diluted with water (20 mL). The solution was basified with 0.880 ammonia and extracted into ethyl acetate (100 mL). The extract was dried over magnesium sulfate and concentrated. The crude product was purified by chromatography on silica using methanol/ethyl acetate (1/9) to afford the titled compound as a solid (70 mg).

Workup

  1. extractionextracted into ethyl acetate (100 mL)
  2. dry with materialThe extract was dried over magnesium sulfate
  3. concentrationconcentrated
  4. customThe crude product was purified by chromatography on silica

Sources & evidence

ORD record
ord-cf8de84d06b04181b7b8564b4982ecba
Source dataset
uspto-grants-2012_06
Patent number
US08193239B2

Reaction notes

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