Ethyl orthoformate → HCID 59238170, compound

HRID 2068573Notes

Reaction equation

HRID 2068573 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[CH:20]=[CH:19][C:18]([NH2:21])=[C:17]([C:22](=[O:29])[NH:23][CH2:24][C:25]([O:27][CH3:28])=[O:26])[CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:30](OC(OCC)OCC)C>>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[CH:16]=[C:17]3[C:18](=[CH:19][CH:20]=2)[N:21]=[CH:30][N:23]([CH2:24][C:25]([O:27][CH3:28])=[O:26])[C:22]3=[O:29])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

3

Reactant 2

HCID 31214Ethyl orthoformateHCID 59238187HCID 59238187, compound

Product 1

HCID 59238170HCID 59238170, compound

Procedure

4-[4-Amino-3-(methoxycarbonylmethyl-carbamoyl)-phenyl]-[1,4]diazepane-1-carboxylic acid tert-butyl ester (30.6 g) was treated with 375 mL of triethylorthoformate at 125° C. with stirring for 18 hours. At this time, reaction mixture was concentrated in vacuo and the resulting residue was taken up in ethyl acetate and water. The organic phase was washed thrice with 10% KHSO4 aqueous solution, once with water, once with brine. The organic layer was then dried over magnesium sulfate and was filtered. The filtrate was concentrated in vacuo. The product was purified by flash column chromatography (500 g of silica) eluting with 60% to 70% ethyl acetate in hexane. Appropriate fractions were collected and evaporated to dryness. The resulting residue was dissolved in diethyl ether and re-evaporated; this dissolution and re-evaporated was repeated using pentane. All solids obtained as foams were pooled, resulting in a total yield of 15.56 g of 4-(3-methoxycarbonylmethyl-4-oxo-3,4-dihydro-quinazolin-6-yl)-[1,4]diazepane-1-carboxylic acid tert-butyl ester.

Workup

  1. customAt this time, reaction mixture
  2. concentrationwas concentrated in vacuo
  3. washThe organic phase was washed thrice with 10% KHSO4 aqueous solution
  4. dry with materialThe organic layer was then dried over magnesium sulfate
  5. filtrationwas filtered
  6. concentrationThe filtrate was concentrated in vacuo
  7. customThe product was purified by flash column chromatography (500 g of silica)
  8. washeluting with 60% to 70% ethyl acetate in hexane
  9. customAppropriate fractions were collected
  10. customevaporated to dryness
  11. dissolutionThe resulting residue was dissolved in diethyl ether
  12. customre-evaporated
  13. dissolutionthis dissolution
  14. customre-evaporated
  15. customAll solids obtained as foams

Sources & evidence

ORD record
ord-ef750483c0e24b2eb9266ae0c034e2e7
Source dataset
uspto-grants-2012_10
Patent number
US08299023B2

Reaction notes

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