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

HRID 2382048Notes

Reaction equation

HRID 2382048 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]1[CH:20]=[C:21]2[C:25](=[CH:26][CH:27]=1)[N:24]([NH2:28])[CH:23]=[C:22]2[CH2:29][CH2:30][C:31]1[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=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:18][C:19]1[CH:20]=[C:21]2[C:25](=[CH:26][CH:27]=1)[N:24]([NH:28][C:15]([C:11]1[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]=1)=[O:17])[CH:23]=[C:22]2[CH2:29][CH2:30][C:31]1[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=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 68552093HCID 68552093, compound

Product 1

HCID 592000522-(3-Fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid [5-fluoro-3-(2-pyridin-3-yl-ethyl)-indol-1-yl]-amideYield 1.3%

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 (232 mg, 1 mmol) and 5-fluoro-3-(2-pyridin-3-yl-ethyl)-indol-1-ylamine (255 mmol) in DMF (10 mL) is stirred at 50° C. for 10 min. The mixture is treated with DMTMM (276 mg, 1 mmol) and stirred at 50° C. for 0.5 h. The mixture is diluted with saturated aqueous Na2CO3 (50 mL), and extracted with EtOAc (3×50 mL). The combined organic layer is dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by triturating in MeOH:H2O (2:1) to afford 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid [5-fluoro-3-(2-pyridin-3-yl-ethyl)-indol-1-yl]-amide (6 mg, 1%). MS: 470 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 9.21 (s, 1H), 8.51 (m, 1H), 8.40 (m, 1H), 8.33 (d, 1H), 8.19 (d, 1H), 7.74 (d, 1H), 7.63 (m, 1H), 7.45 (m, 4H), 7.33 (m, 1H), 7.06 (m, 1H), 3.29 (s, 2H), 3.01 (s, 2H), 2.77 (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 purified
  6. customby triturating in MeOH:H2O (2:1)

Sources & evidence

ORD record
ord-45ca778fc8c6437d95e9f767e94786b9
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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