Ammonia → 2-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-3-fluorophenyl)cyclohexyl)acetic acid

HRID 2237626Notes

Reaction equation

HRID 2237626 reaction equation
Cl[C:2]1[C:7]2[C:8](=[O:31])[N:9]([C:13]3[CH:18]=[CH:17][C:16]([CH:19]4[CH2:24][CH2:23][CH:22]([CH2:25][C:26]([O:28]C)=[O:27])[CH2:21][CH2:20]4)=[CH:15][C:14]=3[F:30])[CH2:10][CH2:11][O:12][C:6]=2[N:5]=[CH:4][N:3]=1.[Li+].[OH-].Cl.C(O)(C)C.[NH3:39]>O1CCOCC1.C1COCC1.CO.O.C(Cl)Cl>[NH2:39][C:2]1[C:7]2[C:8](=[O:31])[N:9]([C:13]3[CH:18]=[CH:17][C:16]([CH:19]4[CH2:20][CH2:21][CH:22]([CH2:25][C:26]([OH:28])=[O:27])[CH2:23][CH2:24]4)=[CH:15][C:14]=3[F:30])[CH2:10][CH2:11][O:12][C:6]=2[N:5]=[CH:4][N:3]=1

Participants

9

Reactant 5

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 3776IsopropanolHCID 3939Lithium HydroxideHCID 59302529methyl 2-(4-(4-(4-chloro-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-3-fluorophenyl)cyclohexyl)acetate

Product 1

HCID 593025262-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-3-fluorophenyl)cyclohexyl)acetic acid

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolventHCID 21892291Methanol tetrahydrofuran waterSolvent

Conditions

Temperature
23 °C

Procedure

The title compound was prepared as follows. A mixture of methyl 2-(4-(4-(4-chloro-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-3-fluorophenyl)cyclohexyl)acetate (20 mg, 0.045 mmol), from Preparation 4, in 0.5M ammonia in dioxane was stirred at 50° C., in a tightly capped flask, for 3 hours. The reaction mixture was concentrated to give a white solid, which was carried on to the next step without further purification. LiOH (4.5 mg, 0.18 mmol) was added to a solution of the white solid in THF/methanol/water (2.4 mL, 3:2:1) and the resulting solution was stirred at 23° C. for 16 hours. 1M HCl solution was added to reaction solution to adjust the pH about 3. 20% i-propanol in DCM (30 mL) was added to extract reaction mixture. The organic layer was separated and dried over MgSO4 and concentrated to give a solid. Purification was done by chromatography (4 g, silica gel column) with methanol/DCM from 2-6% to give a white solid 12 mg as the title compound.

Workup

  1. customfrom Preparation 4
  2. concentrationThe reaction mixture was concentrated
  3. customto give a white solid, which
  4. customwas carried on to the next step without further purification
  5. extractionto extract
  6. customreaction mixture
  7. customThe organic layer was separated
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. customto give a solid
  11. customPurification

Sources & evidence

ORD record
ord-1e8f50ea10b04d3e95bed99987a192bb
Source dataset
uspto-grants-2010_05
Patent number
US07718645B2

Reaction notes

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