Diisopropylethylamine → (r)-3-{(s)-2-[2-(2-Fluoro-phenyl)-acetylamino]-3-methyl-pentanoylamino}-8-trifluoromethyl-2,3,4,9-tetrahydro-1h-carbazole-3-carboxylic acid ((s)-1-methoxycarbamoyl-2-methyl-butyl)-amide

HRID 45409Notes

Reaction equation

HRID 45409 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([NH:11][C@@H:12]([CH:36]([CH3:39])[CH2:37][CH3:38])[C:13]([NH:15][C:16]1([C:33]([OH:35])=O)[CH2:28][C:27]2[C:26]3[C:21](=[C:22]([C:29]([F:32])([F:31])[F:30])[CH:23]=[CH:24][CH:25]=3)[NH:20][C:19]=2[CH2:18][CH2:17]1)=[O:14])=[O:10].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH3:73][O:74][NH:75][C:76](=[O:83])[C@@H:77]([NH2:82])[CH:78]([CH3:81])[CH2:79][CH3:80]>CN(C=O)C>[CH3:73][O:74][NH:75][C:76]([C@@H:77]([NH:82][C:33]([C@:16]1([NH:15][C:13](=[O:14])[C@@H:12]([NH:11][C:9](=[O:10])[CH2:8][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[F:1])[CH:36]([CH3:39])[CH2:37][CH3:38])[CH2:28][C:27]2[C:26]3[C:21](=[C:22]([C:29]([F:32])([F:30])[F:31])[CH:23]=[CH:24][CH:25]=3)[NH:20][C:19]=2[CH2:18][CH2:17]1)=[O:35])[CH:78]([CH3:81])[CH2:79][CH3:80])=[O:83]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 64974902HCID 64974902, compoundHCID 68747487HCID 68747487, compound

Product 1

HCID 57617370(r)-3-{(s)-2-[2-(2-Fluoro-phenyl)-acetylamino]-3-methyl-pentanoylamino}-8-trifluoromethyl-2,3,4,9-tetrahydro-1h-carbazole-3-carboxylic acid ((s)-1-methoxycarbamoyl-2-methyl-butyl)-amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

0.500 g (0.91 mmol) of (R/S)-3-{(S)-2-[2-(2-Fluoro-phenyl)-acetylamino]-3-methyl-pentanoylamino}-8-trifluoromethyl-2,3,4,9-tetrahydro-1H-carbazole-3-carboxylic acid (synthesized in according to WO 2006/005484), 0.521 g (1.37 mmol) of HATU and 2.0 mL (11.76 mmol) of DIPEA were dissolved in DMF and stirred for 30 min at room temperature. 0.220 g (1.37 mmol) of (S)-2-Amino-3-methyl-pentanoic acid methoxy-amide were added and the reaction mixture and heated at 110° C. for 3 h. The solvent was removed under vacuum and the residue was purified by high performance liquid chromatography.

Workup

  1. temperaturethe reaction mixture and heated at 110° C. for 3 h
  2. customThe solvent was removed under vacuum
  3. customthe residue was purified by high performance liquid chromatography

Sources & evidence

ORD record
ord-a96e0ffefca34888bde7fbd8d4c00687
Source dataset
uspto-grants-2013_09
Patent number
US08541462B2

Reaction notes

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