Dimethylamine → 1-Allyl-4-{2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}-1H-pyrrole-2-carboxylic acid dimethylamide

HRID 244438Notes

Reaction equation

HRID 244438 reaction equation
[CH2:1]([N:4]1[CH:8]=[C:7]([C:9]([C:15]2[CH:16]=[C:17]3[C:21](=[CH:22][CH:23]=2)[N:20]([C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)[N:19]=[CH:18]3)([OH:14])[C:10]([F:13])([F:12])[F:11])[CH:6]=[C:5]1[C:31](O)=[O:32])[CH:2]=[CH2:3].[CH2:34]([N:36](CC)[CH2:37]C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CNC>CN(C=O)C.[Cl-].[Na+].O.O>[CH3:34][N:36]([CH3:37])[C:31]([C:5]1[N:4]([CH2:1][CH:2]=[CH2:3])[CH:8]=[C:7]([C:9]([C:15]2[CH:16]=[C:17]3[C:21](=[CH:22][CH:23]=2)[N:20]([C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)[N:19]=[CH:18]3)([OH:14])[C:10]([F:11])([F:12])[F:13])[CH:6]=1)=[O:32]

Participants

8

Reactant 4

HCID 674DimethylamineHCID 8471TriethylamineHCID 2724699PyBOPHCID 249590961-Allyl-4-{2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}-1H-pyrrole-2-carboxylic acid

Product 1

HCID 249590951-Allyl-4-{2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}-1H-pyrrole-2-carboxylic acid dimethylamideYield 84%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of 1-allyl-4-{2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}-1H-pyrrole-2-carboxylic acid (400 mg, 0.87 mmol, 1 equiv.) in 10 ml of DMF was added 0.22 mL of triethylamine (1.7 mmol, 2 equiv.) and PyBOP (500 mg, 0.96 mmol, 1.1 equiv.) followed by dimethylamine (2 M in THF, 1.3 mL, 2.6 mmol, 3 equiv.). After 18 hours, the mixture was diluted with 50 mL of brine and 50 mL of water and extracted with ethyl ether. The combined organic layers were dried, filtered, and concentrated in vacuo. The residue was purified by flash chromatography using EtOAc-hexanes (10-60% gradient) to afford 354 mg (84%) of the title compound as a white solid. MS m/z 487.29 (MH+).

Workup

  1. extractionextracted with ethyl ether
  2. customThe combined organic layers were dried
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-7fbca7e5cd7f4f2684dc99d71ce8fa68
Source dataset
uspto-grants-2014_02
Patent number
US08658637B2

Reaction notes

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