Water → HCID 46917868, compound

HRID 516350Notes

Reaction equation

HRID 516350 reaction equation
[F:1][CH:2]([F:35])[C:3]1[N:7]([C:8]2[N:13]=[C:12]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[N:11]=[C:10]([NH:20][CH:21]3[CH2:24][N:23]([S:25]([CH3:28])(=[O:27])=[O:26])[CH2:22]3)[N:9]=2)[C:6]2[CH:29]=[CH:30][CH:31]=[C:32]([O:33][CH3:34])[C:5]=2[N:4]=1.[H-].[Na+].I[CH3:39].O>CN(C=O)C>[F:35][CH:2]([F:1])[C:3]1[N:7]([C:8]2[N:13]=[C:12]([N:14]3[CH2:15][CH2:16][O:17][CH2:18][CH2:19]3)[N:11]=[C:10]([N:20]([CH3:39])[CH:21]3[CH2:22][N:23]([S:25]([CH3:28])(=[O:27])=[O:26])[CH2:24]3)[N:9]=2)[C:6]2[CH:29]=[CH:30][CH:31]=[C:32]([O:33][CH3:34])[C:5]=2[N:4]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 46917867HCID 46917867, compound

Product 1

HCID 46917868HCID 46917868, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of 4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-N-[1-(methylsulfonyl)-3-azetidinyl]-6-(4-morpholinyl)-1,3,5-triazin-2-amine (Example 28) (170 mg, 0.33 mmol) in DMF (4 mL) at 0° C. was added NaH (24 mg, 1.0 mmol). The mixture was stirred for 30 min at this temperature and iodomethane (0.3 mL, excess) was added. The resulting mixture was allowed to warm to 20° C. and stirred for 2 hrs. Water was added and the resulting precipitate was filtered, washed with water, and dried. Recrystallization from CH2Cl2/MeOH gave 4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-N-methyl-N-[1-(methylsulfonyl)-3-azetidinyl]-6-(4-morpholinyl)-1,3,5-triazin-2-amine (156 mg, 89% yield): mp (CH2Cl2/MeOH) 242-244° C.; 1H NMR (DMSO-d6) δ7.97-7.60 (m, 2H), 7.42 (t, J=8.1 Hz, 1H), 6.96 (d, J=7.9 Hz, 1H), 5.50 and 5.26 (2m, 1H), 4.17-4.12 (m, 4H), 3.98 (s, 3H), 3.81 (m, 4H), 3.71-3.69 (m, 4H), 3.24 (s, 3H), 3.09 (s, 3H); Anal. Calcd. for C21H26F2N8O4S: C, 48.1; H, 5.0; N, 21.3. Found: C, 48.0; H, 5.0; N, 21.3%.

Workup

  1. additionwas added
  2. filtrationthe resulting precipitate was filtered
  3. washwashed with water
  4. customdried
  5. customRecrystallization from CH2Cl2/MeOH

Sources & evidence

ORD record
ord-4e145a97d8d2477aa817a1166f3239df
Source dataset
uspto-grants-2015_08
Patent number
US09108980B2

Reaction notes

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