Diisopropylcarbodiimide → 1-[4-(3-Cyclopentyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yloxymethyl)-phenyl]-1-pyrrolidin-yl-methanone

HRID 641486Notes

Reaction equation

HRID 641486 reaction equation
[CH:1]1([N:6]2[CH2:12][CH2:11][C:10]3[CH:13]=[C:14]([O:17][CH2:18][C:19]4[CH:27]=[CH:26][C:22]([C:23](O)=[O:24])=[CH:21][CH:20]=4)[CH:15]=[CH:16][C:9]=3[CH2:8][CH2:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(N=C=NC(C)C)(C)C.O.ON1C2C=CC=CC=2N=N1.[NH:48]1[CH2:52][CH2:51][CH2:50][CH2:49]1>ClCCl.CN(C)C=O>[CH:1]1([N:6]2[CH2:12][CH2:11][C:10]3[CH:13]=[C:14]([O:17][CH2:18][C:19]4[CH:27]=[CH:26][C:22]([C:23]([N:48]5[CH2:52][CH2:51][CH2:50][CH2:49]5)=[O:24])=[CH:21][CH:20]=4)[CH:15]=[CH:16][C:9]=3[CH2:8][CH2:7]2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

7

Reactant 4

HCID 12734DiisopropylcarbodiimideHCID 31268PyrrolidineHCID 27960291-Hydroxybenzotriazole hydrateHCID 103614874-(3-Cyclopentyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yloxymethyl)-benzoic acid

Product 1

HCID 104321781-[4-(3-Cyclopentyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yloxymethyl)-phenyl]-1-pyrrolidin-yl-methanone

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

4-(3-Cyclopentyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yloxymethyl)-benzoic acid (E89) (0.201 mg, 0.55 mmol)), 1,3-diisopropylcarbodiimide (44 μl, 0.6 mmol) and 1-hydroxybenzotriazole hydrate (82 mg, 0.6 mmol) were dissolved in a mixture of dichloromethane (2 ml) and dimethyl formamide (1 ml). After stirring at room temperature for 0.5 hours, pyrrolidine (41 μl, 0.5 mmol) was added and the resulting mixture was allowed to stir for 16 hours. The crude reaction was applied to a SCX ion exchange cartridge (Varian bond-elute, 5 g) and washed with methanol and then a mixture of 0.880 ammonia:methanol (1:9). The combined basic fractions were concentrated in vacuo, and the resulting residue was purified by column chromatography eluting with a mixture of 0.880 ammonia:ethanol:dichloromethane (1:9:90) to afford the title compound (E90); MS (ES+) m/e 419 [M+H]+.

Workup

  1. stirringto stir for 16 hours
  2. customThe crude reaction
  3. washwashed with methanol
  4. additiona mixture of 0.880 ammonia:methanol (1:9)
  5. concentrationThe combined basic fractions were concentrated in vacuo
  6. customthe resulting residue was purified by column chromatography
  7. washeluting with a mixture of 0.880 ammonia:ethanol:dichloromethane (1:9:90)

Sources & evidence

ORD record
ord-452411afe2e349f8ac956877409ec20f
Source dataset
uspto-grants-2010_04
Patent number
US07696193B2

Reaction notes

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