Ethyl 3-methoxybenzimidate → HCID 59511775, compound

HRID 1157461Notes

Reaction equation

HRID 1157461 reaction equation
[NH2:1][C:2]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][C@@H:20]([CH3:23])[CH2:21][OH:22])=[CH:14][C:3]=1[C:4]([NH:6][CH2:7][C:8](=[O:13])[NH:9][CH:10]([CH3:12])[CH3:11])=[O:5].[CH3:24][O:25][C:26]1[CH:27]=[C:28]([CH:34]=[CH:35][CH:36]=1)[C:29](=N)OCC>C(O)C.C(OCC)(=O)C>[OH:22][CH2:21][C@H:20]([CH3:23])[CH2:19][O:18][C:15]1[CH:14]=[C:3]2[C:2](=[CH:17][CH:16]=1)[N:1]=[C:29]([C:28]1[CH:34]=[CH:35][CH:36]=[C:26]([O:25][CH3:24])[CH:27]=1)[N:6]([CH2:7][C:8]([NH:9][CH:10]([CH3:12])[CH3:11])=[O:13])[C:4]2=[O:5]

Participants

5

Reactant 2

HCID 12282162Ethyl 3-methoxybenzimidateHCID 59511757HCID 59511757, compound

Product 1

HCID 59511775HCID 59511775, compoundYield 47.1%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of crude (S)-(+)-2-amino-5-(3-hydroxy-2-methylpropoxy)-N-(isopropylcarbamoylmethyl)benzamide (INTERMEDIATE VII.1) (223 mg, 0.70 mmol) (prepared in Procedure VIII) and ethyl 3-methoxybenzimidate*HCl (INTERMEDIATE III.2) (449 mg, 2.08 mmol) in anhydrous ethanol (5 mL) was heated to 80° C. in a tightly capped scintillation vial for 16 h. This was then cooled and concentrated in vacuo. The crude residue was partitioned between dichloromethane/2-propanol (3:1, v/v) and water and the aqueous extracted with further dichloromethane/2-propanol (3:1, v/v). The combined organics were dried (MgSO4), filtered and concentrated in vacuo. The crude solid thus obtained was suspended in cold ethyl acetate and collected by filtration affording (S)-(+)-2-[6-(3-hydroxy-2-methylpropoxy)-2-(3-methoxyphenyl)-4-oxo-4H-quinazolin-3-yl]-N-isopropylacetamide (145 mg, 0.33 mmol, 43% from 2-amino-5-[(S)-(+)-3-hydroxy-2-methylpropoxy]benzoic acid) as a light brown solid.

Workup

  1. temperatureThis was then cooled
  2. concentrationconcentrated in vacuo
  3. customThe crude residue was partitioned between dichloromethane/2-propanol (3:1
  4. extractionv/v) and water and the aqueous extracted with further dichloromethane/2-propanol (3:1
  5. dry with materialThe combined organics were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude solid thus obtained
  9. filtrationcollected by filtration

Sources & evidence

ORD record
ord-286d4bda9f6c49428898b4c1daddf91d
Source dataset
uspto-grants-2010_10
Patent number
US07807686B2

Reaction notes

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