4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride → 4-Methyl-[2,2']bipyrimidinyl-5-carboxylic acid (6-trifluoromethyl-indol-1-yl)-amide

HRID 2382068Notes

Reaction equation

HRID 2382068 reaction equation
[CH3:1][C:2]1[C:7]([C:8]([OH:10])=O)=[CH:6][N:5]=[C:4]([C:11]2[N:16]=[CH:15][CH:14]=[CH:13][N:12]=2)[N:3]=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:8]([C:7]2[C:2]([CH3:1])=[N:3][C:4]([C:11]3[N:16]=[CH:15][CH:14]=[CH:13][N:12]=3)=[N:5][CH:6]=2)=[O:10])=[CH:21][CH:20]=1

Participants

6

Reactant 3

HCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 616999854-Methyl-2-(pyrimidin-2-yl)pyrimidine-5-carboxylic acidHCID 685531851H-Indol-1-amine, 6-(trifluoromethyl)-

Product 1

HCID 591999464-Methyl-[2,2']bipyrimidinyl-5-carboxylic acid (6-trifluoromethyl-indol-1-yl)-amideYield 25.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 4-methyl-[2,2′]bipyrimidinyl-5-carboxylic acid (259 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-[2,2′]bipyrimidinyl-5-carboxylic acid (6-trifluoromethyl-indol-1-yl)-amide (100 mg, 25%). MS: 399 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 12.16 (s, NH, 1H), 9.39 (s, 1H), 9.06 (d, 2H), 7.92 (s, 1H), 7.81 (m, 2H), 7.70 (t, 1H), 7.44 (d, 1H), 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-1580fd5aa718431297d82ec796f8a272
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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