Acetic Acid → tert-Butyl 4-[N-[-2-Acetoxymethyl-4-oxo-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl]-N-methylamino]benzoate

HRID 47861Notes

Reaction equation

HRID 47861 reaction equation
[C:1]([O:4][CH2:5][C:6]1[N:15]([CH2:16][O:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[C:14](=[O:24])[C:13]2[C:8](=[CH:9][C:10]3[CH2:27][CH2:26][CH:25]([NH:28][C:29]4[CH:41]=[CH:40][C:32]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])=[CH:31][CH:30]=4)[C:11]=3[CH:12]=2)[N:7]=1)(=[O:3])[CH3:2].[C:42](O)(=O)C.C=O.C([BH3-])#N.[Na+]>C1COCC1>[C:1]([O:4][CH2:5][C:6]1[N:15]([CH2:16][O:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[C:14](=[O:24])[C:13]2[C:8](=[CH:9][C:10]3[CH2:27][CH2:26][CH:25]([N:28]([C:29]4[CH:41]=[CH:40][C:32]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])=[CH:31][CH:30]=4)[CH3:42])[C:11]=3[CH:12]=2)[N:7]=1)(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 22744292tert-Butyl 4-[N-[2-Acetoxymethyl-4-oxo-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl]amino]benzoate

Product 1

HCID 22744296tert-Butyl 4-[N-[-2-Acetoxymethyl-4-oxo-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl]-N-methylamino]benzoateYield 98%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of tert-butyl 4-[N-[-2-acetoxymethyl-4-oxo-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl]amino]benzoate (0.060 g, 0.106 mmol) in THF (6 ml) was added glacial acetic acid (2 ml) followed by 37% aqueous formaldehyde (0.090 ml). The solution was stirred for 2.5 hours at room temperature and then sodium cyanoborohydride (0.017 g, 0.27 mmol) was added. The reaction mixture was stirred overnight at room temperature. The solvent was removed in vacuo and the residue was partitioned between ethyl acetate (25 ml) and water (25 ml). The aqueous layer was extracted with more ethyl acetate (2×25 ml). The combined organics were washed with saturated aqueous sodium bicarbonate (30 ml), brine (30 ml), dried (Na2SO4) and concentrated in vacuo to leave an oil (0.060 g, 98%); 1H-NMR (CDCl3) 1.20 (s, 9H, POM C(CH3)3), 1.58 (s, 9H, CO2C(CH3)3), 2.15 (s, 3H, CH3CO), 2.02, 2.52 (2×m, 2H, 7-CH2), 2.74 (s, 3H, N10-Me), 3.13 (m, 2H, 8-CH2) 5.21 (s, 2H, 2-CH2), 5.66 (t, 1H, J=8.1 Hz, 6-H), 6.12 (AB system, J=10.8 Hz, 2H, POM CH2), 6.85 (d, J=8.8 Hz, 2H, 3,5′-ArH), 7.58 (s, 1H, 9-H), 7.90 (d, J=8.9 Hz, 2H, 2,6′-ArH), 8.08 (s, 1H, 5-H); MS (ESI, m/z) 578 (M+H)+.

Workup

  1. stirringThe reaction mixture was stirred overnight at room temperature
  2. customThe solvent was removed in vacuo
  3. customthe residue was partitioned between ethyl acetate (25 ml) and water (25 ml)
  4. extractionThe aqueous layer was extracted with more ethyl acetate (2×25 ml)
  5. washThe combined organics were washed with saturated aqueous sodium bicarbonate (30 ml), brine (30 ml)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-188d9472e81f4eb9846f596b43e1126c
Source dataset
uspto-grants-2004_03
Patent number
US06699861B1

Reaction notes

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