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

HRID 1714940Notes

Reaction equation

HRID 1714940 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-96ad29d255fd48a8a2ec52a3c9df4f0c
Source dataset
uspto-grants-2010_09
Patent number
US07799773B2

Reaction notes

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