Ammonia → (S)-4-Amino-N-(1-cyano-2-(4-(1-methyl-2-oxoindolin-6-yl)phenyl)ethyl)tetrahydro-2H-pyran-4-carboxamide

HRID 216952Notes

Reaction equation

HRID 216952 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:19]=[C:18]3[C:14]([CH2:15][C:16](=[O:21])[N:17]3[CH3:20])=[CH:13][CH:12]=2)=[CH:7][CH:6]=1)#[N:2].N>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:10]=[CH:9][C:8]([C:11]3[CH:19]=[C:18]4[C:14]([CH2:15][C:16](=[O:21])[N:17]4[CH3:20])=[CH:13][CH:12]=3)=[CH:7][CH:6]=2)=[O:24])[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1

Participants

4

Reactant 2

HCID 222AmmoniaHCID 59568567(S)-tert-Butyl 4-(1-cyano-2-(4-(1-methyl-2-oxoindolin-6-yl)phenyl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

Product 1

HCID 49783830(S)-4-Amino-N-(1-cyano-2-(4-(1-methyl-2-oxoindolin-6-yl)phenyl)ethyl)tetrahydro-2H-pyran-4-carboxamideYield 35.4%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

A solution of (S)-tert-butyl 4-(1-cyano-2-(4-(1-methyl-2-oxoindolin-6-yl)phenyl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 21, step (ii), 35 mg) in formic acid (5 mL) was stirred at 50° C. for 30 min. The reaction mixture was poured into ice/water (50 mL) and basified to pH 8 with 0.880 aqueous ammonia solution. The mixture was extracted with ethyl acetate (2×40 mL) and the organics were dried over sodium sulfate and evaporated in vacuo. The crude product was purified by reversed phase HPLC on a Waters' Sunfire column using methanol and aqueous 0.1% trifluoroacetic acid as eluent. The fractions containing the desired compound were evaporated to dryness to afford product which was further purified by chromatography on silica eluting with 3% 2M methanolic ammonia in dichloromethane. Pure fractions were evaporated to dryness to afford the titled compound (10 mg).

Workup

  1. extractionThe mixture was extracted with ethyl acetate (2×40 mL)
  2. dry with materialthe organics were dried over sodium sulfate
  3. customevaporated in vacuo
  4. customThe crude product was purified by reversed phase HPLC on a Waters' Sunfire column
  5. additionThe fractions containing the desired compound
  6. customwere evaporated to dryness
  7. customto afford product which
  8. customwas further purified by chromatography on silica eluting with 3% 2M methanolic ammonia in dichloromethane
  9. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-2024f3fa202c45c7b939c360d03d3607
Source dataset
uspto-grants-2012_06
Patent number
US08193239B2

Reaction notes

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