Diisopropylethylamine → 4-Methyl-2-(3-fluoro-phenyl)-pyrimidine-5-carboxylic acid (5-nitro-indol-1-yl)-amide

HRID 2382109Notes

Reaction equation

HRID 2382109 reaction equation
CCN(C(C)C)C(C)C.[F:10][C:11]1[CH:12]=[C:13]([C:17]2[N:22]=[C:21]([CH3:23])[C:20]([C:24]([OH:26])=O)=[CH:19][N:18]=2)[CH:14]=[CH:15][CH:16]=1.[N+:27]([C:30]1[CH:31]=[C:32]2[C:36](=[CH:37][CH:38]=1)[N:35]([NH2:39])[CH:34]=[CH:33]2)([O-:29])=[O:28].CN(C(SC1[N+]([O-])=CC=CC=1)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[N+:27]([C:30]1[CH:31]=[C:32]2[C:36](=[CH:37][CH:38]=1)[N:35]([NH:39][C:24]([C:20]1[C:21]([CH3:23])=[N:22][C:17]([C:13]3[CH:14]=[CH:15][CH:16]=[C:11]([F:10])[CH:12]=3)=[N:18][CH:19]=1)=[O:26])[CH:34]=[CH:33]2)([O-:29])=[O:28]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 10571248(Dimethylamino)-N,N-dimethyl((1-oxo-1lambda~5~-pyridin-2-yl)sulfanyl)methaniminium hexafluorophosphateHCID 105834305-nitro-1H-indol-1-amineHCID 617025872-(3-Fluorophenyl)-4-methylpyrimidine-5-carboxylic acid

Product 1

HCID 591999564-Methyl-2-(3-fluoro-phenyl)-pyrimidine-5-carboxylic acid (5-nitro-indol-1-yl)-amideYield 44.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

DIPEA (12.65 mmol) is added a solution of 2-(3-fluoro-phenyl) -4-methyl-pyrimidine-5-carboxylic acid (4.22 mmol), 5-nitro-indole-1-ylamine (4.22 mmol) and HOTT (S-(1-oxido-2-pyridyl)-thio-N,N,N′,N′-tetramethyluronium hexafluorophosphate) (7.6 mmol) in anhydrous DMF (15 mL) and the mixture is heated at 80-90° C. overnight. After evaporation of solvent, the residue is dissolved in EtOAc (150 mL), washed with water (20 mL), 5% sodium sulfate (20 mL), water (mL) and brine (20 mL). The organic layer is dried (Na2SO4), filtered and concentrated. The residue is kept at rt overnight to yield 4-methyl-2-(3-fluoro-phenyl)-pyrimidine-5-carboxylic acid (5-nitro-indol-1-yl)-amide (730 mg, 44%) as a solid. MS: 392 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 2.78(s, 3H), 6.88(d, H), 7.38-7.53(m, H), 7.57-7.76(m, 2H), 7.81(d, H), 8.06-8.32(m, 2H), 8.34(d, H), 8.65(d, H), 9.27(s, 2H).

Workup

  1. customAfter evaporation of solvent
  2. dissolutionthe residue is dissolved in EtOAc (150 mL)
  3. washwashed with water (20 mL), 5% sodium sulfate (20 mL), water (mL) and brine (20 mL)
  4. dry with materialThe organic layer is dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-aa3a52373ad44850a91487a3d7bd01b7
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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