4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride → 2-(3-Fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (6-trifluoromethyl-indol-1-yl)-amide

HRID 2382066Notes

Reaction equation

HRID 2382066 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.[F:18][C:19]([F:31])([F:30])[C:20]1[CH:28]=[C:27]2[C:23]([CH:24]=[CH:25][N:26]2[NH2:29])=[CH:22][CH:21]=1.C[N+]1(C2N=C(OC)N=C(OC)N=2)CCOCC1.[Cl-]>CN(C=O)C.C([O-])([O-])=O.[Na+].[Na+]>[F:31][C:19]([F:18])([F:30])[C:20]1[CH:28]=[C:27]2[C:23]([CH:24]=[CH:25][N:26]2[NH:29][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:22][CH:21]=1

Participants

6

Reactant 3

HCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 617025872-(3-Fluorophenyl)-4-methylpyrimidine-5-carboxylic acidHCID 685531851H-Indol-1-amine, 6-(trifluoromethyl)-

Product 1

HCID 591999662-(3-Fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (6-trifluoromethyl-indol-1-yl)-amideYield 44%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (278 mg, 1.2 mmol) and 6-trifluoromethyl-indol-1-ylamine (200 mg, 1 mmol) in DMF (5 mL) is stirred at 50° C. for 0.5 h. The mixture is treated with DMTMM (290 mg, 1.05 mmol) and stirred at 50° C. for 1 h. The mixture is diluted with saturated aqueous Na2CO3 (5 mL) and extracted with EtOAc (3×50 mL). The combined organic layer is dried (Na2SO4), filtered and concentrated in vacuo. The residue is triturated with Et2O/heptane overnight. The precipitate is collected by filtration, washed with H2O (50 mL) and heptane (50 mL), and dried in vacuo to afford 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (6-trifluoromethyl-indol-1-yl)-amide (180 mg, 44%). MS: 415 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 12.09 (s, NH, 1H), 9.33 (s, 1H), 8.35 (d, 1H), 8.20 (d, 1H), 7.90 (s, 1H), 7.79 (m, 2H), 7.65 (m, 1H), 7.46 (m, 2H), 6.74 (d, 1H), 2.79 (s, 3H).

Workup

  1. extractionextracted with EtOAc (3×50 mL)
  2. dry with materialThe combined organic layer is dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue is triturated with Et2O/heptane overnight
  6. filtrationThe precipitate is collected by filtration
  7. washwashed with H2O (50 mL) and heptane (50 mL)
  8. customdried in vacuo

Sources & evidence

ORD record
ord-b344cfdb46bd4a1ebee7ab7a05774484
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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