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

HRID 2382067Notes

Reaction equation

HRID 2382067 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[N:12]=[C:11]([CH3:13])[C:10]([C:14]([OH:16])=O)=[CH:9][N:8]=1.[F:17][C:18]([F:30])([F:29])[C:19]1[CH:27]=[C:26]2[C:22]([CH:23]=[CH:24][N:25]2[NH2:28])=[CH:21][CH:20]=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:30][C:18]([F:17])([F:29])[C:19]1[CH:27]=[C:26]2[C:22]([CH:23]=[CH:24][N:25]2[NH:28][C:14]([C:10]2[C:11]([CH3:13])=[N:12][C:7]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)=[N:8][CH:9]=2)=[O:16])=[CH:21][CH:20]=1

Participants

6

Reactant 3

HCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 617020254-Methyl-2-(pyridin-2-yl)pyrimidine-5-carboxylic acidHCID 685531851H-Indol-1-amine, 6-(trifluoromethyl)-

Product 1

HCID 591999544-Methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid (6-trifluoromethyl-indol-1-yl)-amideYield 40.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 2-(2-pyridyl)-4-methyl-pyrimidine-5-carboxylic acid (258 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 4-methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid (6-trifluoromethyl-indol-1-yl)-amide (160 mg, 40%). MS: 398 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 12.13 (s, NH, 1H), 9.36 (s, 1H), 8.82 (d, 1H), 8.48 (d, 1H), 8.04 (m, 1H), 7.83 (m, 3H), 7.60 (m, 1H), 7.44 (d, 1H), 6.74 (d, 1H), 2.80 (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-8cac0778d55d4306a535dcda0be99d0b
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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