Diisopropylethylamine → HCID 86722063, compound

HRID 525046Notes

Reaction equation

HRID 525046 reaction equation
[NH2:1][N:2]1[CH:6]=[CH:5][C:4]([Br:7])=[C:3]1[C:8]([NH:10][C:11]1[CH:16]=[C:15]([F:17])[CH:14]=[C:13]([F:18])[CH:12]=1)=[O:9].[CH2:19]([O:26][C@H:27]1[CH2:31][N:30]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[C@H:29]([C:39](O)=[O:40])[CH2:28]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(N(C(C)C)CC)(C)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>CN(C)C=O.O>[CH2:19]([O:26][C@H:27]1[CH2:31][N:30]([C:32]([O:34][C:35]([CH3:36])([CH3:37])[CH3:38])=[O:33])[C@H:29]([C:39](=[O:40])[NH:1][N:2]2[CH:6]=[CH:5][C:4]([Br:7])=[C:3]2[C:8](=[O:9])[NH:10][C:11]2[CH:16]=[C:15]([F:17])[CH:14]=[C:13]([F:18])[CH:12]=2)[CH2:28]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 11860409Boc-Hyp(Bzl)-OHHCID 70978853HCID 70978853, compound

Product 1

HCID 86722063HCID 86722063, compoundYield 74.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

1-Amino-3-bromo-N-(3,5-difluorophenyl)-1H-pyrrole-2-carboxamide (1.5 g, 4.75 mmol), (2S,4R)-4-(benzyloxy)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid (0.99 g, 3.08 mmol) and diisopropylethylamine (2.8 ml, 16.08 mmol) were dissolved in dimethylformamide (30 ml) and the mixture cooled at 0° C. To this mixture, T3P (50% solution in ethyl acetate, 2.1 ml, 7.19 mmol) dissolved in DMF (5 ml) was dropwise added. Once the addition is over, the mixture was stirred at room temperature for 48 h. To this mixture, water was added and extracted twice with ethyl acetate. The organic phase was washed with water and brine, dried over sodium sulphate, filtered and the solvents evaporated under reduced pressure. The residue was purified by flash chromatography (0% to 25% hexanes/AcOEt) to yield 1.42 g (74% yield) of the title compound.

Workup

  1. additionwas dropwise added
  2. additionOnce the addition
  3. extractionextracted twice with ethyl acetate
  4. washThe organic phase was washed with water and brine
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. customthe solvents evaporated under reduced pressure
  8. customThe residue was purified by flash chromatography (0% to 25% hexanes/AcOEt)

Sources & evidence

ORD record
ord-76a02780c1864bdb86a2f29529021f95
Source dataset
uspto-grants-2016_05
Patent number
US09340547B2

Reaction notes

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