Morpholine → HCID 68515979, compound

HRID 641990Notes

Reaction equation

HRID 641990 reaction equation
[CH:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][N:7]([C:13]1[CH:14]=[C:15]([CH:20]=[CH:21][C:22]=1[CH3:23])[C:16]([O:18][CH3:19])=[O:17])[C:6]2=[O:24])=O.[NH:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.O.C(Cl)Cl.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[CH3:23][C:22]1[CH:21]=[CH:20][C:15]([C:16]([O:18][CH3:19])=[O:17])=[CH:14][C:13]=1[N:7]1[C:6](=[O:24])[C:5]2[C:10](=[CH:11][CH:12]=[C:3]([CH2:1][N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[CH:4]=2)[N:9]=[CH:8]1

Participants

7

Reactant 3

HCID 8083MorpholineHCID 5049666Sodium triacetoxyborohydrideHCID 86630235HCID 86630235, compound

Product 1

HCID 68515979HCID 68515979, compound

Reagents, catalysts & solvents 3

HCID 11026Titanium isopropoxideCatalystHCID 6344DichloromethaneSolventHCID 21908982Water methylene chlorideSolvent

Procedure

To a solution of methyl 3-(6-formyl-4-oxoquinazolin-3(4H)-yl)-4-methylbenzoate (0.60 g) and titanium isopropoxide (1.10 ml) in methylene chloride (15 ml) was added morpholine (0.33 ml). The reaction was stirred at room temperature for 1 hour, then sodium triacetoxyborohydride (0.80 g) was added and stirred for a further 16 hours. The reaction mixture was diluted with water/methylene chloride (1:1) and filtered through diatomaceous earth (Celite®). The layers were separated, the aqueous layer extracted with methylene chloride. The combined organics were dried (magnesium sulphate) and concentrated to give a solid. The solid was purified by column chromatography on a silica column using initially methylene chloride and then a 19:1 mixture of methylene chloride and methanol as eluent to give methyl 4-methyl-3-[6-(morpholin-4-ylmethyl)-4-oxoquinazolin-3(4H)-yl]benzoate as a solid (0.62 g). NMR Spectrum: (DMSOd6) 2.18 (s, 3H), 2.40 (m, 4H), 3.59 (m, 4H), 3.63 (s, 2H), 3.87 (s, 3H), 7.62 (d, 1H), 7.75 (d, 1H), 7.85 (m, 1H), 8.03 (m, 2H), 8.12 (d, 1H), 8.28 (s, 1H); Mass Spectrum: M+H+ 394.

Workup

  1. stirringstirred for a further 16 hours
  2. filtrationfiltered through diatomaceous earth (Celite®)
  3. customThe layers were separated
  4. extractionthe aqueous layer extracted with methylene chloride
  5. dry with materialThe combined organics were dried (magnesium sulphate)
  6. concentrationconcentrated
  7. customto give a solid
  8. customThe solid was purified by column chromatography on a silica column
  9. additiona 19:1 mixture of methylene chloride and methanol as eluent

Sources & evidence

ORD record
ord-497e7bc21e6542b197202706b3525c01
Source dataset
uspto-grants-2010_04
Patent number
US07696215B2

Reaction notes

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