Diisopropylethylamine → 2-(3-Fluorophenyl)-4-methylpyrimidine-5-carboxylic acid-(3-dimethylsulfamoyl-5-fluoroindol-1-yl)amide

HRID 2381931Notes

Reaction equation

HRID 2381931 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([CH3:14])[C:11]([C:15]([OH:17])=O)=[CH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.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.[CH3:51][N:52]([CH3:67])[S:53]([C:56]1[C:64]2[C:59](=[CH:60][CH:61]=[C:62]([F:65])[CH:63]=2)[N:58]([NH2:66])[CH:57]=1)(=[O:55])=[O:54]>CN(C=O)C>[CH3:51][N:52]([CH3:67])[S:53]([C:56]1[C:64]2[C:59](=[CH:60][CH:61]=[C:62]([F:65])[CH:63]=2)[N:58]([NH:66][C:15]([C:11]2[C:12]([CH3:14])=[N:13][C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=3)=[N:9][CH:10]=2)=[O:17])[CH:57]=1)(=[O:54])=[O:55]

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 617025872-(3-Fluorophenyl)-4-methylpyrimidine-5-carboxylic acidHCID 685564591-amino-5-fluoro-1H-indole-3-sulfonic acid dimethylamide

Product 1

HCID 250995862-(3-Fluorophenyl)-4-methylpyrimidine-5-carboxylic acid-(3-dimethylsulfamoyl-5-fluoroindol-1-yl)amideYield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-(3-fluorophenyl)-4-methylpyrimidine-5-carboxylic acid (116 mg) and HATU (190 mg) in dry DMF is treated with DIPEA (0.09 mL) and stirred at rt for 40 min. 1-Amino-5-fluoro-1H-indole-3-sulfonic acid dimethylamide (192 mg) is added and the mixture is stirred at rt for 24 h. The mixture is concentrated in vacuo. The residue is dissolved in EtOAc, washed with 2 N aqueous NaOH, water and brine, dried (MgSO4) and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 30% EtOAc/heptane to afford 2-(3-fluorophenyl)-4-methylpyrimidine-5-carboxylic acid-(3-dimethylsulfamoyl-5-fluoroindol-1-yl)amide (85 mg, 40%) as a solid. MS: 472 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 2.68 (s, 6H), 2.79 (s, 3H), 7.25-7.35 (m, 1H), 7.45-7.55 (m, 1H), 7.57-7.80 (m, 3H), 8.20 (d, 1H), 8.35 (s, 1H), 8.47 (s, 2H), 9.28 (s, 1H), 12.40 (s, 1H).

Workup

  1. stirringthe mixture is stirred at rt for 24 h
  2. concentrationThe mixture is concentrated in vacuo
  3. dissolutionThe residue is dissolved in EtOAc
  4. washwashed with 2 N aqueous NaOH, water and brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue is purified by silica gel chromatography
  8. washeluting with 30% EtOAc/heptane

Sources & evidence

ORD record
ord-95b7bdc7dc5c461ba98f440e6a149e53
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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