Morpholine → tert-Butyl 4-[N-[7-Chloro-3-methyl-2-morpholinomethyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]benzoate

HRID 47854Notes

Reaction equation

HRID 47854 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:19])[N:7]([CH3:18])[C:8]([CH2:12]OS(C)(=O)=O)=[N:9]2)=[CH:4][C:3]=1[CH2:20][N:21]([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)[CH2:22][C:23]#[CH:24].[NH:38]1[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1>ClCCl>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:19])[N:7]([CH3:18])[C:8]([CH2:12][N:38]3[CH2:43][CH2:42][O:41][CH2:40][CH2:39]3)=[N:9]2)=[CH:4][C:3]=1[CH2:20][N:21]([C:25]1[CH:26]=[CH:27][C:28]([C:29]([O:31][C:32]([CH3:33])([CH3:35])[CH3:34])=[O:30])=[CH:36][CH:37]=1)[CH2:22][C:23]#[CH:24]

Participants

4

Reactant 2

HCID 8083MorpholineHCID 11813583tert-Butyl 4-[N-[7-Chloro-2-methanesulphonyloxymethyl-3-methyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]benzoate

Product 1

HCID 11813508tert-Butyl 4-[N-[7-Chloro-3-methyl-2-morpholinomethyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]benzoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of tert-butyl 4-[N-[7-chloro-2-methanesulphonyloxymethyl-3-methyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl )amino]benzoate (0.193 g, 0.35 mmol), dichloromethane (7 ml), and morpholine (0.304 g, 3.5 mmol) was stirred at room temperature for 6 h under argon. The cloudy reaction mixture was then partitioned between ethyl acetate (200 ml) and 5% aqueous sodium carbonate (80 ml). The organic layer was washed more 5% sodium carbonate (2×80 ml), and brine (80 ml), dried (Na2SO4) and concentrated in vacuo. Purification by column chromatography, on elution with 10% ethyl acetate in dichloromethane, afforded a solid which was triturated with 5% dichloromethane in hexanes. The white solid was collected by filtration, dried in vacuo over P2O5 (0.174 g, 82%), mp 140-143° C.; 1H-NMR (DMSO-d6) 1.50 (s, 9H, But), 2.48, (br s obscured) and 3.55 (br s) (8H, N(CH2CH2)2O), 3.62 (s, 5H, 2-CH2, N3-Me), 3.20 (s(poorly resolved triplet), 1H, C≡CH), 4.39 (s, 2H, CH2C≡C), 4.79 (s, 2H, 6-CH2), 6.78 (d, J=8.7 Hz, 2H, 3′,5′-ArH), 7.72 (d, J=8.7 Hz, 2H, 2′,6′-ArH), 7.80, 7.89 (2×s, 2H, 5-H, 8-H). MS (ESI, m/z) 537, 539 [(M+H)+, 100%, 38% respectively; Cl isotopic pattern].

Workup

  1. customThe cloudy reaction mixture
  2. customwas then partitioned between ethyl acetate (200 ml) and 5% aqueous sodium carbonate (80 ml)
  3. washThe organic layer was washed more 5% sodium carbonate (2×80 ml), and brine (80 ml)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customPurification by column chromatography
  7. washon elution with 10% ethyl acetate in dichloromethane
  8. customafforded a solid which
  9. customwas triturated with 5% dichloromethane in hexanes
  10. filtrationThe white solid was collected by filtration
  11. dry with materialdried in vacuo over P2O5 (0.174 g, 82%), mp 140-143° C.

Sources & evidence

ORD record
ord-d7002b11359a4b74ae68563be41d1b59
Source dataset
uspto-grants-2004_03
Patent number
US06699861B1

Reaction notes

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