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

HRID 2382062Notes

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.[CH2:18]([C:20]1[C:28]2[C:23](=[CH:24][CH:25]=[C:26]([O:29][C:30]([F:33])([F:32])[F:31])[CH:27]=2)[N:22]([NH2:34])[CH:21]=1)[CH3:19].C[N+]1(C2N=C(OC)N=C(OC)N=2)CCOCC1.[Cl-]>CN(C=O)C.C([O-])([O-])=O.[Na+].[Na+]>[CH2:18]([C:20]1[C:28]2[C:23](=[CH:24][CH:25]=[C:26]([O:29][C:30]([F:31])([F:33])[F:32])[CH:27]=2)[N:22]([NH:34][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:21]=1)[CH3:19]

Participants

Conditions

Temperature: 50 °C

Procedure

A solution of 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (250 mg, 1.1 mmol) and 3-ethyl-5-trifluoromethoxy-indol-1-ylamine (244 mg, 1 mmol) in DMF (5 mL) is stirred at 50° C. for 1 h. The mixture is treated with DMTMM (276 mg, 1 mmol) and stirred at 50° C. for 1 h. The mixture is diluted with saturated aqueous Na2CO3 (5 mL) and stirred for 10 min. 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 (3-ethyl-5-trifluoromethoxy-indol-1-yl)-amide (270 mg, 59%). MS: 459 (M+H); 1H NMR (300 MHz, CDCl3): δ 11.51 (s, NH, 1H), 9.08 (s, 1H), 8.35 (d, 1H), 8.24 (d, 1H), 7.48 (m, 2H), 7.22 (m, 2H), 7.11 (m, 2H), 2.85 (s, 3H), 2.80 (q, 2H), 1.35 (t, 3H).

Workup

stirringstirred for 10 min
filtrationThe precipitate is collected by filtration
washwashed with H2O (50 mL) and heptane (50 mL)
customdried in vacuo

Sources & evidence

ORD record: ord-dec2f4e1fc1241ae83cd89360c3bddd2
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08258130B2

Reaction notes

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