3,5-Difluoroaniline → (S)-tert-Butyl 4-(benzyloxy)-1-(3-bromo-2-(3,5-difluorophenylcarbamoyl)-1H-pyrrol-1-ylamino)-1-oxobutan-2-ylcarbamate

HRID 1052362Notes

Reaction equation

HRID 1052362 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][C@H:11]([NH:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C:12]([NH:14][N:15]1[CH:19]=[CH:18][C:17]([Br:20])=[C:16]1[C:21]([O:23]C)=O)=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:33][C:34]1[CH:35]=[C:36]([CH:38]=[C:39]([F:41])[CH:40]=1)[NH2:37].C[Al](C)C>>[CH2:1]([O:8][CH2:9][CH2:10][C@H:11]([NH:25][C:26](=[O:27])[O:28][C:29]([CH3:30])([CH3:32])[CH3:31])[C:12]([NH:14][N:15]1[CH:19]=[CH:18][C:17]([Br:20])=[C:16]1[C:21](=[O:23])[NH:37][C:36]1[CH:35]=[C:34]([F:33])[CH:40]=[C:39]([F:41])[CH:38]=1)=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 965953,5-DifluoroanilineHCID 16682925TrimethylaluminumHCID 86722060(S)-Methyl 1-(4-(benzyloxy)-2-(tert-butoxycarbonylamino)butanamido)-3-bromo-1H-pyrrole-2-carboxylate

Product 1

HCID 86722061(S)-tert-Butyl 4-(benzyloxy)-1-(3-bromo-2-(3,5-difluorophenylcarbamoyl)-1H-pyrrol-1-ylamino)-1-oxobutan-2-ylcarbamateYield 45.8%

Procedure

(S)-Methyl 1-(4-(benzyloxy)-2-((tert-butoxycarbonyl)amino)butanamido)-3-bromo-1H-pyrrole-2-carboxylate (4 g, 7.84 mmol) was treated with 3,5-difluoroaniline (5.06 g, 39.19 mmol) and trimethyl aluminium (2 M in toluene, 19.6 mL, 39.18 mmol) according to the method of Preparation 10a. The residue was purified using SP1® Purification System (0% to 50% hexane-ethyl acetate) to obtain 2.18 g (41% yield) of the title compound as a white solid. Purity 88%.

Workup

  1. customThe residue was purified
  2. customSP1® Purification System (0% to 50% hexane-ethyl acetate)

Sources & evidence

ORD record
ord-4409cf765198458d939a57401d258a95
Source dataset
uspto-grants-2016_07
Patent number
US09388189B2

Reaction notes

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