Potassium Carbonate → HCID 66698086, compound

HRID 516362Notes

Reaction equation

HRID 516362 reaction equation
[F:1][CH:2]([F:37])[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]([N:20]3[CH2:25][CH2:24][CH:23]([NH:26][S:27]([CH3:30])(=[O:29])=[O:28])[CH2:22][CH2:21]3)[N:9]=2)[C:6]2[CH:31]=[CH:32][CH:33]=[C:34]([O:35][CH3:36])[C:5]=2[N:4]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:45][CH2:46][CH2:47][OH:48]>CN(C=O)C.O>[F:37][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]3[CH2:21][CH2:22][CH:23]([N:26]([CH2:45][CH2:46][CH2:47][OH:48])[S:27]([CH3:30])(=[O:29])=[O:28])[CH2:24][CH2:25]3)[N:9]=2)[C:6]2[CH:31]=[CH:32][CH:33]=[C:34]([O:35][CH3:36])[C:5]=2[N:4]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 123083-Bromo-1-propanolHCID 46917723HCID 46917723, compound

Product 1

HCID 66698086HCID 66698086, compoundYield 49%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

To a mixture of N-{1-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-4-piperidinyl}methanesulfonamide (Example 17) (1.95 g, 3.62 mmol) and K2CO3 (6 g, excess) in DMF (20 mL) was added 3-bromo-1-propanol (4 mL, excess). The reaction mixture was stirred at 20° C. for 7 days and diluted with water. The resulting sticky material was extracted into CH2Cl2 (4×30 mL) and dried (Na2SO4). Evaporation of the solvent and the chromatography of the residue on silica, eluting with a gradient of CH2Cl2 and EtOAc (0-20%) followed by CH2Cl2/MeOH (97:3) gave N-{1-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-4-piperidinyl}-N-(3-hydroxypropyl)methanesulfonamide (1.04 g, 49%): mp (CH2Cl2/MeOH) 219-221° C.; 1H NMR (DMSO-d6) δ7.89 (d, J=8.2 Hz, 1H), 7.69 (t, JHF=52.9 Hz, 1H), 7.41 (t, J=8.2 Hz, 1H), 6.95 (d, J=7.9 Hz, 1H), 4.73 (d, J=12.8 Hz, 1H), 4.82 (d, J=12.3 Hz, 1H), 4.44 (t, J=5.1 Hz, 1H), 3.97 (S, 3H), 3.92-3.83 (m, 1H), 3.80-3.79 (m, 4H), 3.69 (m, 4H), 3.40-3.32 (m, 2H), 3.14-2.96 (m, 4H), 3.96 (s, 3H), 1.87-1.80 (m, 2H), 1.74-1.64 (m, 4H); Anal Calcd. for C25H34F2N8O5S: C, 50.33; H, 5.74; N, 18.78. Found: C, 50.2; H, 5.9; N, 18.5%.

Workup

  1. extractionThe resulting sticky material was extracted into CH2Cl2 (4×30 mL)
  2. dry with materialdried (Na2SO4)
  3. customEvaporation of the solvent
  4. washthe chromatography of the residue on silica, eluting with a gradient of CH2Cl2 and EtOAc (0-20%)

Sources & evidence

ORD record
ord-3b2bb05bc3954c6fba7d21d61a0c82b5
Source dataset
uspto-grants-2015_08
Patent number
US09108980B2

Reaction notes

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