Trifluoroacetic acid → (S)-N-((2S,3S)-1-Acetyl-5-((1-(2-cyanophenyl)-1H-indazol-3-yl)methyl)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl)-2-(methylamino)propanamide

HRID 1486064Notes

Reaction equation

HRID 1486064 reaction equation
[C:1]([N:4]1[C@@H:10]([CH3:11])[C@H:9]([NH:12][C:13](=[O:25])[C@@H:14]([N:16](C)[C:17](=O)OC(C)(C)C)[CH3:15])[C:8](=[O:26])[N:7]([CH2:27][C:28]2[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[N:30]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=3[C:43]#[N:44])[N:29]=2)[C:6]2[CH:45]=[CH:46][CH:47]=[CH:48][C:5]1=2)(=[O:3])[CH3:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[C:1]([N:4]1[C@@H:10]([CH3:11])[C@H:9]([NH:12][C:13](=[O:25])[C@@H:14]([NH:16][CH3:17])[CH3:15])[C:8](=[O:26])[N:7]([CH2:27][C:28]2[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[N:30]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=3[C:43]#[N:44])[N:29]=2)[C:6]2[CH:45]=[CH:46][CH:47]=[CH:48][C:5]1=2)(=[O:3])[CH3:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 118292660tert-butyl(S)-1-((2S,3S)-1-acetyl-5-((1-(2-cyanophenyl)-1H-indazol-3-yl)methyl)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate

Product 1

HCID 73425656(S)-N-((2S,3S)-1-Acetyl-5-((1-(2-cyanophenyl)-1H-indazol-3-yl)methyl)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl)-2-(methylamino)propanamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a rt solution of tert-butyl(S)-1-((2S,3S)-1-acetyl-5-((1-(2-cyanophenyl)-1H-indazol-3-yl)methyl)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (79 mg, 122 μmol) in CH2Cl2 (486 μl) was added TFA (122 μl). The reaction was stirred for 1.5 h, then concentrated and purified by reverse phase preparative HPLC to provide, after extraction from sat. aq. NaHCO3, (S)-N-((2S,3S)-1-acetyl-5-((1-(2-cyanophenyl)-1H-indazol-3-yl)methyl)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl)-2-(methylamino)propanamide (57.0 mg, 85%) as a white solid. MS m/z 550 (MH)+.

Workup

  1. concentrationconcentrated
  2. custompurified by reverse phase preparative HPLC
  3. customto provide
  4. extractionafter extraction from sat. aq. NaHCO3, (S)-N-((2S,3S)-1-acetyl-5-((1-(2-cyanophenyl)-1H-indazol-3-yl)methyl)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl)-2-(methylamino)propanamide (57.0 mg, 85%) as a white solid

Sources & evidence

ORD record
ord-78623dc078f24cf3af90f720f461da0a
Source dataset
uspto-grants-2016_08
Patent number
US09422331B2

Reaction notes

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