Diisopropylethylamine → (S)-tert-butyl 2-allyl-3-(2-(3-(3-bromo-5-fluorophenyl)-1-methoxy-1-oxopropan-2-ylamino)-2-oxoethyl)-1H-indole-1-carboxylate

HRID 1471648Notes

Reaction equation

HRID 1471648 reaction equation
[CH2:1]([C:4]1[N:5]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:6]2[C:11]([C:12]=1[CH2:13][C:14](O)=[O:15])=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH:2]=[CH2:3].Cl.[NH2:25][C@@H:26]([CH2:31][C:32]1[CH:37]=[C:36]([F:38])[CH:35]=[C:34]([Br:39])[CH:33]=1)[C:27]([O:29][CH3:30])=[O:28].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>C(Cl)Cl>[CH2:1]([C:4]1[N:5]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:6]2[C:11]([C:12]=1[CH2:13][C:14]([NH:25][C@@H:26]([CH2:31][C:32]1[CH:37]=[C:36]([F:38])[CH:35]=[C:34]([Br:39])[CH:33]=1)[C:27]([O:29][CH3:30])=[O:28])=[O:15])=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH:2]=[CH2:3]

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 90280217(S)-methyl 2-amino-3-(3-bromo-5-fluorophenyl)propanoate hydrochlorideHCID 902812522-(2-allyl-1-(tert-butoxycarbonyl)-1H-indol-3-yl)acetic acid

Product 1

HCID 90281512(S)-tert-butyl 2-allyl-3-(2-(3-(3-bromo-5-fluorophenyl)-1-methoxy-1-oxopropan-2-ylamino)-2-oxoethyl)-1H-indole-1-carboxylateYield 65.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-(2-allyl-1-(tert-butoxycarbonyl)-1H-indol-3-yl)acetic acid (850 mg, 2.7 mmol) and (S)-methyl 2-amino-3-(3-bromo-5-fluorophenyl)propanoate hydrochloride (720 mg, 2.61 mmol) were combined in DCM (13 mL) and treated with HATU (1.49 g, 3.9 mmol) and iPr2NEt (1.13 mL, 6.5 mmol). After stirring for 16 h at room temperature, the reaction was partitioned between DCM and H2O. The organics were separated and dried over sodium sulfate. After removal of solvent, the crude product was purified by silica gel chromatography to provide (S)-tert-butyl 2-allyl-3-(2-(3-(3-bromo-5-fluorophenyl)-1-methoxy-1-oxopropan-2-ylamino)-2-oxoethyl)-1H-indole-1-carboxylate (0.98 g, 63%). MS (m/z) 573 [M+H]+.

Workup

  1. customthe reaction was partitioned between DCM and H2O
  2. customThe organics were separated
  3. dry with materialdried over sodium sulfate
  4. customAfter removal of solvent
  5. customthe crude product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-22085af253ca44158aa15914e9964284
Source dataset
uspto-grants-2015_04
Patent number
US09012441B2

Reaction notes

Loading…