Benzoic acid, 4-amino-, 1,1-dimethylethyl ester → tert-Butyl 4-[N-((6RS)-2-(2,2-dimethylpropionyloxymethyl)-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]benzoate

HRID 450008Notes

Reaction equation

HRID 450008 reaction equation
[CH3:1][C:2]([CH3:23])([CH3:22])[C:3]([O:5][CH2:6][C:7]1[NH:16][C:15](=[O:17])[C:14]2[C:9](=[CH:10][C:11]3[CH2:20][CH2:19][C:18](=O)[C:12]=3[CH:13]=2)[N:8]=1)=[O:4].[NH2:24][C:25]1[CH:37]=[CH:36][C:28]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[CH:27][CH:26]=1.[B][B][B][B][B][B][B][B][B][B]>CO.C(Cl)Cl>[CH3:22][C:2]([CH3:23])([CH3:1])[C:3]([O:5][CH2:6][C:7]1[NH:16][C:15](=[O:17])[C:14]2[C:9](=[CH:10][C:11]3[CH2:20][CH2:19][CH:18]([NH:24][C:25]4[CH:37]=[CH:36][C:28]([C:29]([O:31][C:32]([CH3:33])([CH3:34])[CH3:35])=[O:30])=[CH:27][CH:26]=4)[C:12]=3[CH:13]=2)[N:8]=1)=[O:4]

Participants

6

Reactant 3

HCID 233272Benzoic acid, 4-amino-, 1,1-dimethylethyl esterHCID 1360652992-(2,2dimethylpropionyloxymethyl)-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-4,6-dioneHCID 178419135HCID 178419135, compound

Product 1

HCID 136065302tert-Butyl 4-[N-((6RS)-2-(2,2-dimethylpropionyloxymethyl)-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]benzoateYield 58.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A suspension of 2-(2,2-dimethylpropionyloxymethyl)-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-4,6-dione (0.47 g, 1.50 mmol) in anhydrous methanol (33 ml) and anhydrous CH2Cl2 (5 ml) was treated with tert-butyl 4-aminobenzoate (0.34 g, 1.78 mmol) followed by decaborane (0.07 g, 0.58 mmol) and the mixture stirred at room temperature under argon for 18 h. The solvent was removed in vacuo and the residue purified by column chromatography (50 g of silica gel) eluting with 30% ethyl acetate in CH2Cl2 to yield the desired product as a white solid (0.43 g, 58%); m.p. 231° C.; 1H-NMR (CDCl3) δ 1.26 (s, 9H, CMe3), 1.58 (s, 9H, CO2CMe3), 2.00 (m, 1H, 7-H), 2.72 (m, 1H, 7-H), 3.08 (m, 2H, 8-H), 5.10 (s, 2H, 2-CH2), 5.15 (m, 1H, 6-H), 6.67 (d, J=8.8 Hz, 2H, 3′-H, 5′-H), 7.58 (s, 1H, 9-H), 7.87 (d, J=8.8 Hz, 2H, 2′-H, 6′-H), 8.24 (s, 1H, 5-H); MS (FAB, m/z). Found 491 [(M+H)+, 25%], 514 [(M+Na)+, 100%]. Found C, 68.37; H, 6.86; N, 8.35. C28H33N3O5 requires C, 68.41; H, 6.77; N, 8.55%.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue purified by column chromatography (50 g of silica gel)
  3. washeluting with 30% ethyl acetate in CH2Cl2

Sources & evidence

ORD record
ord-4117b453b6ba42f6bcf4c0611e3520fe
Source dataset
uspto-grants-2013_07
Patent number
US08486955B2

Reaction notes

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