Ammonium Chloride → HCID 178454139, compound

HRID 1403151Notes

Reaction equation

HRID 1403151 reaction equation
[I-].[C:2]([O:6][C:7]([NH:9][C@H:10]([C:16]([NH:18][C@H:19]1[CH2:24][CH2:23][C@H:22]([O:25][C:26]2[CH:31]=[C:30]([N:32]3[C:36]4[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=4[N:34]=[C:33]3[CH:41]([F:43])[F:42])[N:29]=[C:28]([N:44]3[CH2:49][CH2:48][O:47][CH2:46][CH2:45]3)[N:27]=2)[CH2:21][CH2:20]1)=[O:17])[CH2:11][CH2:12][S+](C)C)=[O:8])([CH3:5])([CH3:4])[CH3:3].[Cl-].[NH4+]>O1CCCC1>[C:2]([O:6][C:7](=[O:8])[NH:9][C@H:10]1[CH2:11][CH2:12][N:18]([C@H:19]2[CH2:24][CH2:23][C@H:22]([O:25][C:26]3[CH:31]=[C:30]([N:32]4[C:36]5[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=5[N:34]=[C:33]4[CH:41]([F:43])[F:42])[N:29]=[C:28]([N:44]4[CH2:49][CH2:48][O:47][CH2:46][CH2:45]4)[N:27]=3)[CH2:21][CH2:20]2)[C:16]1=[O:17])([CH3:5])([CH3:4])[CH3:3]

Participants

4

Reactant 2

HCID 25517Ammonium ChlorideHCID 178503678HCID 178503678, compound

Product 1

HCID 178454139HCID 178454139, compoundYield 21.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

[(3S)-3-[(tert-Butoxycarbonyl)amino]-4-{[trans-4-({6-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-2-(morpholin-4-yl)pyrimidin-4-yl}oxy)cyclohexyl]amino}-4-oxobutyl](dimethyl)sulfonium iodide (919 mg) was dissolved in tetrahydrofuran (9.2 mL), and cooled to 0° C. under a nitrogen air flow, and a 1.6 M solution (0.7 mL) of hexamethyldisilazanelithium in tetrahydrofuran was added dropwise thereto, followed by stirring at 0° C. for 2 hours. A 1.6 M solution (0.7 mL) of hexamethyldisilazanelithium in tetrahydrofuran was further added dropwise thereto, followed by stirring at 0° C. for 1 hour. A saturated aqueous ammonium chloride solution was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=70:30-0:100) to obtain tert-butyl{(3S)-1-[trans-4-({6-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-2-(morpholin-4-yl)pyrimidin-4-yl}oxy)cyclohexyl]-2-oxopyrrolidin-3-yl}carbamate (154 mg).

Workup

  1. stirringby stirring at 0° C. for 1 hour
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (hexane:ethyl acetate=70:30-0:100)

Sources & evidence

ORD record
ord-2c7bf6d64d33484ba759b6dbd8b94068
Source dataset
uspto-grants-2014_12
Patent number
US08912180B2

Reaction notes

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