Ammonia → (S)-4-Amino-N-(1-cyano-2-(4-(2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)phenyl)ethyl)tetrahydro-2H-pyran-4-carboxamide

HRID 216986Notes

Reaction equation

HRID 216986 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]=[CH:13][C:14]3[O:18][C:17](=[O:19])[NH:16][C:15]=3[CH:20]=2)=[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]=[CH:13][C:14]4[O:18][C:17](=[O:19])[NH:16][C:15]=4[CH:20]=3)=[CH:9][CH:10]=2)=[O:23])[CH2:25][CH2:26][O:27][CH2:28][CH2:29]1

Participants

5

Reactant 2

HCID 222AmmoniaHCID 59568584(S)-tert-Butyl 4-(1-cyano-2-(4-(2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)phenyl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

Product 1

HCID 59568558(S)-4-Amino-N-(1-cyano-2-(4-(2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)phenyl)ethyl)tetrahydro-2H-pyran-4-carboxamide

Reagents, catalysts & solvents 2

HCID 284Formic AcidSolventHCID 962WaterSolvent

Procedure

(S)-tert-Butyl 4-(1-cyano-2-(4-(2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)phenyl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 33, step (ii), 160 mg) was heated at 50° C. in formic acid (0.5 mL) for 10 min. The cooled solution was diluted with water (50 mL) and basified with ‘880’ ammonia and the resulting precipitate extracted into ethyl acetate (200 mL). The dried extract was concentrated to dryness and purified purified by reversed phase HPLC (using a SunFire column) eluting with methanol/0.1% aqueous trifluoroacetic acid. The pure fractions were freeze dried to afford the titled compound as a trifluoroacetatic acid salt (36 mg) TFA salt as a colourless solid.

Workup

  1. extractionthe resulting precipitate extracted into ethyl acetate (200 mL)
  2. extractionThe dried extract
  3. concentrationwas concentrated to dryness
  4. custompurified
  5. custompurified by reversed phase HPLC (
  6. washeluting with methanol/0.1% aqueous trifluoroacetic acid
  7. customdried

Sources & evidence

ORD record
ord-38eb457326b84c719fa57a4cba17d14b
Source dataset
uspto-grants-2012_06
Patent number
US08193239B2

Reaction notes

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