Water → HCID 178423376, compound

HRID 1403153Notes

Reaction equation

HRID 1403153 reaction equation
[F:1][CH:2]([F:40])[C:3]1[N:7]([C:8]2[CH:13]=[C:12]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][C@@H:15]3[CH3:20])[N:11]=[C:10]([NH:21][CH2:22][C@H:23]3[CH2:28][CH2:27][C@H:26]([NH:29][CH2:30][C:31]([CH3:34])([OH:33])[CH3:32])[CH2:25][CH2:24]3)[N:9]=2)[C:6]2[CH:35]=[C:36]([CH3:39])[CH:37]=[CH:38][C:5]=2[N:4]=1.N1([C:46](N2C=CN=C2)=[O:47])C=CN=C1.C(N(CC)CC)C.O>O1CCCC1>[F:40][CH:2]([F:1])[C:3]1[N:7]([C:8]2[CH:13]=[C:12]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][C@@H:15]3[CH3:20])[N:11]=[C:10]([NH:21][CH2:22][C@H:23]3[CH2:28][CH2:27][C@H:26]([N:29]4[CH2:30][C:31]([CH3:34])([CH3:32])[O:33][C:46]4=[O:47])[CH2:25][CH2:24]3)[N:9]=2)[C:6]2[CH:35]=[C:36]([CH3:39])[CH:37]=[CH:38][C:5]=2[N:4]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 178423377HCID 178423377, compound

Product 1

HCID 178423376HCID 178423376, compoundYield 95.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1-({trans-4-[({4-[2-(Difluoromethyl)-6-methyl-1H-benzimidazol-1-yl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidin-2-yl}amino)methyl]cyclohexyl}amino)-2-methylpropan-2-ol (100 mg) was dissolved in tetrahydrofuran (2 mL), and di-1H-imidazol-1-ylmethanone (131 mg) and triethylamine (50 μL) were added thereto, followed by stirring for 3 hours while heating and refluxing. After the completion of the reaction, water was added thereto, followed by extraction with ethyl acetate. The extracts were washed with saturated brine and dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. The residue was purified by amino silica gel column chromatography (hexane:ethyl acetate=60:40) to obtain 3-{trans-4-[({4-[2-(difluoromethyl)-6-methyl-1H-benzimidazol-1-yl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidin-2-yl}amino)methyl]cyclohexyl}-5,5-dimethyl-1,3-oxazolidin-2-one (100 mg) as a white powder.

Workup

  1. temperaturewhile heating
  2. temperaturerefluxing
  3. additionwas added
  4. extractionfollowed by extraction with ethyl acetate
  5. washThe extracts were washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customthe solvent was evaporated under reduced pressure
  8. customThe residue was purified by amino silica gel column chromatography (hexane:ethyl acetate=60:40)

Sources & evidence

ORD record
ord-ddbe529177b349e2a8c1a9ae636c6064
Source dataset
uspto-grants-2014_12
Patent number
US08912180B2

Reaction notes

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