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

HRID 216943Notes

Reaction equation

HRID 216943 reaction equation
[C:1]([C@@H:3]([NH:22][C:23]([C:25]1([NH:31]C(=O)OC(C)(C)C)[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1)=[O:24])[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])[N:16]([CH3:20])[C:15]=3[CH:21]=2)=[CH:7][CH:6]=1)#[N:2]>C(O)=O>[NH2:31][C:25]1([C:23]([NH:22][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])[N:16]([CH3:20])[C:15]=4[CH:21]=3)=[CH:9][CH:10]=2)=[O:24])[CH2:26][CH2:27][O:28][CH2:29][CH2:30]1

Participants

3

Reactant 1

HCID 59568548(S)-tert-Butyl 4-(1-cyano-2-(4-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)phenyl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

Product 1

HCID 49783826(S)-4-Amino-N-(1-cyano-2-(4-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)phenyl)ethyl)tetrahydro-2H-pyran-4-carboxamideYield 40.1%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

(S)-tert-Butyl 4-(1-cyano-2-(4-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)phenyl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 17, step (ii), 145 mg) (crude mixture) was dissolved in formic acid (3 mL) and the mixture stirred at room temperature for 18 h. The mixture was evaporated to dryness, dissolved in methanol (10 mL), re-evaporated to dryness, dissolved in methanol/acetonitrile 50:50 (4 mL) and purified on reversed phase HPLC eluting with methanol in 0.1% aqueous TFA on a Water's SunFire column. The material was converted to free base by evaporating the relevant fractions, dissolving in ethyl acetate (20 mL) and shaking with saturated aqueous sodium bicarbonate solution (20 mL). The sodium bicarbonate was further extracted with ethyl acetate (20 mL). The combined extracts were dried over magnesium sulfate and evaporated to afford the titled compound (47 mg).

Workup

  1. customThe mixture was evaporated to dryness
  2. dissolutiondissolved in methanol (10 mL)
  3. customre-evaporated to dryness
  4. dissolutiondissolved in methanol/acetonitrile 50:50 (4 mL)
  5. custompurified on reversed phase HPLC
  6. washeluting with methanol in 0.1% aqueous TFA on a Water'
  7. customby evaporating the relevant fractions
  8. dissolutiondissolving in ethyl acetate (20 mL)
  9. stirringshaking with saturated aqueous sodium bicarbonate solution (20 mL)
  10. extractionThe sodium bicarbonate was further extracted with ethyl acetate (20 mL)
  11. dry with materialThe combined extracts were dried over magnesium sulfate
  12. customevaporated

Sources & evidence

ORD record
ord-e9d924bd4ab74b7a9fda4b0b1f80deac
Source dataset
uspto-grants-2012_06
Patent number
US08193239B2

Reaction notes

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