3,3-Dimethyl-1-butanol → (S)-2-{[2-(2-1H-Indazol-4-yl-acetylamino)-4-methyl-thiazole-5-carbonyl]-amino}-3-[(thiophene-2-carbonyl)-amino]propionic acid 3,3-dimethyl-butyl ester

HRID 1952660Notes

Reaction equation

HRID 1952660 reaction equation
[NH:1]1[C:9]2[C:4](=[C:5]([CH2:10][C:11]([NH:13][C:14]3[S:15][C:16]([C:20]([NH:22][C@@H:23]([CH2:27][NH:28][C:29]([C:31]4[S:32][CH:33]=[CH:34][CH:35]=4)=[O:30])[C:24]([OH:26])=[O:25])=[O:21])=[C:17]([CH3:19])[N:18]=3)=[O:12])[CH:6]=[CH:7][CH:8]=2)[CH:3]=[N:2]1.[CH3:36][C:37]([CH3:42])([CH3:41])[CH2:38][CH2:39]O.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>>[CH3:36][C:37]([CH3:42])([CH3:41])[CH2:38][CH2:39][O:25][C:24](=[O:26])[C@@H:23]([NH:22][C:20]([C:16]1[S:15][C:14]([NH:13][C:11](=[O:12])[CH2:10][C:5]2[CH:6]=[CH:7][CH:8]=[C:9]3[C:4]=2[CH:3]=[N:2][NH:1]3)=[N:18][C:17]=1[CH3:19])=[O:21])[CH2:27][NH:28][C:29]([C:31]1[S:32][CH:33]=[CH:34][CH:35]=1)=[O:30]

Participants

4

Reactant 3

HCID 122333,3-Dimethyl-1-butanolHCID 521998p-Toluenesulfonic acid monohydrateHCID 51035164(S)-2-{[2-(2-1H-Indazol-4-yl-acetylamino)-4-methyl-thiazole-5-carbonyl]-amino}-3-[(thiophene-2-carbonyl)-amino]-propionic acid

Product 1

HCID 86671266(S)-2-{[2-(2-1H-Indazol-4-yl-acetylamino)-4-methyl-thiazole-5-carbonyl]-amino}-3-[(thiophene-2-carbonyl)-amino]propionic acid 3,3-dimethyl-butyl esterYield 35.9%

Conditions

Temperature
100 °C

Procedure

A mixture of the (S)-2-{[2-(2-1H-Indazol-4-yl-acetylamino)-4-methyl-thiazole-5-carbonyl]-amino}-3-[(thiophene-2-carbonyl)-amino]-propionic acid (75.3 mg, 0.147 mmole), 3,3-dimethyl-1-butanol (1 mL, 8.054 mmol) and p-toluenesulfonic acid monohydrate (14.1 mg, 0.0741 mmol) was heated at 100° C. for 2½ hours. The reaction is cooled, neutralized and extracted with ethyl acetate (3×15 mL). The organic layers were combined, washed with brine (50 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The resulting crude compound was purified by flash chromatography (80% EtOAc in hexanes) to give (S)-2-{[2-(2-1H-Indazol-4-yl-acetylamino)-4-methyl-thiazole-5-carbonyl]-amino}-3-[(thiophene-2-carbonyl)-amino]propionic acid 3,3-dimethyl-butyl ester (31.5 mg, 35.9%) as a white solid. MS m/e 597.7 (M+H+).

Workup

  1. temperatureThe reaction is cooled
  2. extractionextracted with ethyl acetate (3×15 mL)
  3. washwashed with brine (50 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting crude compound was purified by flash chromatography (80% EtOAc in hexanes)

Sources & evidence

ORD record
ord-a2ba0ccc11dc4437a5469a8c711d6a9e
Source dataset
uspto-grants-2013_03
Patent number
US08404859B2

Reaction notes

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