Morpholine → 3-Cyclobutyl-7-{[4-(4-morpholinyl)-4-oxobutyl]oxy}-2,3,4,5-tetrahydro-1H-3-benzazepine

HRID 222773Notes

Reaction equation

HRID 222773 reaction equation
[CH:1]1([N:5]2[CH2:11][CH2:10][C:9]3[CH:12]=[CH:13][C:14]([O:16][CH2:17][CH2:18][CH2:19][C:20](O)=[O:21])=[CH:15][C:8]=3[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.O.ON1C2C=CC=CC=2N=N1.C1(N=C=N)CCCCC1.[NH:43]1[CH2:48][CH2:47][O:46][CH2:45][CH2:44]1>ClCCl.CN(C)C=O>[CH:1]1([N:5]2[CH2:11][CH2:10][C:9]3[CH:12]=[CH:13][C:14]([O:16][CH2:17][CH2:18][CH2:19][C:20]([N:43]4[CH2:48][CH2:47][O:46][CH2:45][CH2:44]4)=[O:21])=[CH:15][C:8]=3[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 27960291-Hydroxybenzotriazole hydrateHCID 103802614-[(3-Cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]butanoic acidHCID 12048208N-Cyclohexylcarbodiimide

Product 1

HCID 574403143-Cyclobutyl-7-{[4-(4-morpholinyl)-4-oxobutyl]oxy}-2,3,4,5-tetrahydro-1H-3-benzazepine

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

4-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]butanoic acid (E283, Step 1) (0.15 g, 0.50 mmole) was dissolved in dry dichloromethane (5 ml) and dry dimethylformamide (2 ml) was treated with 1-hydroxybenzotriazole hydrate (0.14 g, 1.0 mmole) and N-cyclohexylcarbodiimide, N′-methyl polystyrene HL (0.53 g, 1.0 mmol, 1.7 mmol/g) and stirred for 45 minutes. Morpholine (0.056 ml, 0.65 mmol) was added and the mixture stirred for 3 hours at ambient temperature. The crude reaction mixture was applied to a SCX ion exchange cartridge (Varian bond-elute) and washed with water, methanol and then a mixture of 0.880 ammonia:methanol (1:9). The combined basic fractions were reduced in vacuo. The resulting residue was purified by column chromatography eluting with a mixture of 0.880 ammonia:methanol:dichloromethane (0.5:4.5:95 to 1:9:90) to afford the title compound (E283); MS (ES+) m/e 373 [M+H]+.

Workup

  1. stirringthe mixture stirred for 3 hours at ambient temperature
  2. customThe crude reaction mixture
  3. washwas applied to a SCX ion exchange cartridge (Varian bond-elute)
  4. washwashed with water, methanol
  5. additiona mixture of 0.880 ammonia:methanol (1:9)
  6. customThe resulting residue was purified by column chromatography
  7. washeluting with a mixture of 0.880 ammonia:methanol:dichloromethane (0.5:4.5:95 to 1:9:90)

Sources & evidence

ORD record
ord-31ca2bd630454738821eace549388a4a
Source dataset
uspto-grants-2012_06
Patent number
US08207331B2

Reaction notes

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