Hydrochloric Acid → methyl 2-(4-(4-(4-chloro-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-3-fluorophenyl)cyclohexyl)acetate

HRID 2237623Notes

Reaction equation

HRID 2237623 reaction equation
Cl.[Si]([O:9][CH2:10][CH2:11][N:12]([C:23]1[CH:28]=[CH:27][C:26]([CH:29]2[CH2:34][CH2:33][CH:32]([CH2:35][C:36]([O:38][CH3:39])=[O:37])[CH2:31][CH2:30]2)=[CH:25][C:24]=1[F:40])[C:13]([C:15]1[C:16](Cl)=[N:17][CH:18]=[N:19][C:20]=1[Cl:21])=[O:14])(C(C)(C)C)(C)C>O1CCOCC1.CO>[Cl:21][C:20]1[C:15]2[C:13](=[O:14])[N:12]([C:23]3[CH:28]=[CH:27][C:26]([CH:29]4[CH2:30][CH2:31][CH:32]([CH2:35][C:36]([O:38][CH3:39])=[O:37])[CH2:33][CH2:34]4)=[CH:25][C:24]=3[F:40])[CH2:11][CH2:10][O:9][C:16]=2[N:17]=[CH:18][N:19]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 59302507methyl 2-(4-(4-(N-(2-(tert-butyldimethylsilyloxy) ethyl)-4,6-dichloropyrimidine-5-carboxamido)-3-fluorophenyl)cyclohexyl)acetate

Product 1

HCID 59302529methyl 2-(4-(4-(4-chloro-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-3-fluorophenyl)cyclohexyl)acetate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
23 °C

Procedure

The title compound of Preparation 4 was prepared as follows. 4M HCl in dioxane (0.5 mL) was added to a solution of methyl 2-(4-(4-(N-(2-(tert-butyldimethylsilyloxy)ethyl)-4,6-dichloropyrimidine-5-carboxamido)-3-fluorophenyl)cyclohexyl)acetate (30 mg, 0.05 mmol) in methanol (1 mL). The mixture was stirred at 23° C. for 30 minutes. The reaction mixture was concentrated to remove solvent. The residue was dissolved in acetonitrile (1 mL) and NEt3 (0.05 mL) was added to it. The reaction mixture was stirred at 80° C. for 18 hours. EtOAc (15 mL) and water (15 mL) were added to reaction mixture. The organic layer was separated and dried over MgSO4 and concentrated. The crude material was purified by a 4 g silica gel column eluted with 30-50% EtOAc in heptane to give methyl 2-(4-(4-(4-chloro-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-3-fluorophenyl)cyclohexyl)acetate a colorless oil (20 mg). m/z=448.4 (M+1).

Workup

  1. customwas prepared
  2. concentrationThe reaction mixture was concentrated
  3. customto remove solvent
  4. dissolutionThe residue was dissolved in acetonitrile (1 mL)
  5. additionNEt3 (0.05 mL) was added to it
  6. stirringThe reaction mixture was stirred at 80° C. for 18 hours
  7. additionEtOAc (15 mL) and water (15 mL) were added to reaction mixture
  8. customThe organic layer was separated
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated
  11. customThe crude material was purified by a 4 g silica gel column
  12. washeluted with 30-50% EtOAc in heptane

Sources & evidence

ORD record
ord-1fd7916ab68e4270b654cb8c15aa6210
Source dataset
uspto-grants-2010_05
Patent number
US07718645B2

Reaction notes

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