Hydrazine → (S)-N-((S)-3-amino-4-fluorobutyl)-N-((R)-1-(5-benzyl-2-(2,5-difluorophenyl)thiazol-4-yl)-2,2-dimethylpropyl)-2-hydroxypropanamide

HRID 404846Notes

Reaction equation

C([O:4][C@H:5]([CH3:50])[C:6]([N:8]([C@@H:25]([C:30]1[N:31]=[C:32]([C:42]2[CH:47]=[C:46]([F:48])[CH:45]=[CH:44][C:43]=2[F:49])[S:33][C:34]=1[CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C:26]([CH3:29])([CH3:28])[CH3:27])[CH2:9][CH2:10][C@H:11]([N:14]1C(=O)C2C(=CC=CC=2)C1=O)[CH2:12][F:13])=[O:7])(=O)C.NN>CCO>[NH2:14][C@H:11]([CH2:12][F:13])[CH2:10][CH2:9][N:8]([C@@H:25]([C:30]1[N:31]=[C:32]([C:42]2[CH:47]=[C:46]([F:48])[CH:45]=[CH:44][C:43]=2[F:49])[S:33][C:34]=1[CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C:26]([CH3:28])([CH3:27])[CH3:29])[C:6](=[O:7])[C@@H:5]([OH:4])[CH3:50]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of (R)-1-(((R)-1-(5-benzyl-2-(2,5-difluorophenyl)thiazol-4-yl)-2,2-dimethylpropyl)((S)-3-(1,3-dioxoisoindolin-2-yl)-4-fluorobutyl)amino)-1-oxopropan-2-yl acetate (10 mg, 0.014 mmol) in EtOH (1 mL) was added anhydrous hydrazine (45 μL). The reaction was heated at 60° C. for 14 h. After cooled the reaction mixture, the white precipitate was filtered through Celite® pad with EtOH washes. The filtrate was concentrated and purified by preparative reverse phase HPLC. The pure fractions were combined and lyophilized to yield (S)-N-((S)-3-amino-4-fluorobutyl)-N-((R)-1-(5-benzyl-2-(2,5-difluorophenyl)thiazol-4-yl)-2,2-dimethylpropyl)-2-hydroxypropanamide (2.3 mg, 25%) as TFA salt. LC/MS (uplc) MH+ 543.2, 1.05 min.

Workup

temperatureAfter cooled the reaction mixture
filtrationthe white precipitate was filtered through Celite® pad with EtOH washes
concentrationThe filtrate was concentrated
custompurified by preparative reverse phase HPLC

Sources & evidence

ORD record: ord-2f596ca51b074924a01ebdcaf69aedf6
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08748626B2

Reaction notes

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