1H-Indole-7-carboxylic acid → 1-(7-Indolecarbonyl)-3-(R)-(4-(4fluorophenyl)piperidinylmethyl)-4-(S)-(cyclopropyl)pyrrolidine

HRID 279220Notes

Reaction equation

HRID 279220 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][N:11]([CH2:14][C@H:15]3[C@H:19]([CH:20]4[CH2:22][CH2:21]4)[CH2:18][NH:17][CH2:16]3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[NH:23]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][C:30]=2[C:32](O)=[O:33])[CH:25]=[CH:24]1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[NH:23]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][C:30]=2[C:32]([N:17]2[CH2:18][C@@H:19]([CH:20]3[CH2:21][CH2:22]3)[C@H:15]([CH2:14][N:11]3[CH2:12][CH2:13][CH:8]([C:5]4[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=4)[CH2:9][CH2:10]3)[CH2:16]2)=[O:33])[CH:25]=[CH:24]1

Participants

5

Reactant 2

HCID 742811H-Indole-7-carboxylic acidHCID 187135293-(S)-(4-(4-fluorophenyl)piperidinylmethyl)-4-(S)-(cyclopropyl)pyrrolidine

Product 1

HCID 187135121-(7-Indolecarbonyl)-3-(R)-(4-(4fluorophenyl)piperidinylmethyl)-4-(S)-(cyclopropyl)pyrrolidine

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 0.02 g (0.067 mmol) of 3-(S)-(4-(4-fluorophenyl)piperidinylmethyl)-4-(S)-(cyclopropyl)pyrrolidine and 0.0012 g of (0.01 mmol) dimethylanrinopyridine (DMAP) in 2 mL of CH2Cl2 at rt was added 0.019 g (0.1 mmol) of 1,3-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and 0.016 g (0.1 mmol) of 7-indolecarboxylic acid and the reaction mixture was stirred for 1 h. The reaction mixture was partitioned between ethyl acetate and sat'd NaHCO3 solution. The organic fraction was dried over MgSO4, filtered and the filtrate was concentrated. The residue was purified by chomatography (HPLC Waters Nova-Pak 8×10 RCM 25-40% MeOH in H2O 0.5% TFA) to give the title compound.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate
  2. dry with materialThe organic fraction was dried over MgSO4
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated
  5. customThe residue was purified by chomatography (HPLC Waters Nova-Pak 8×10 RCM 25-40% MeOH in H2O 0.5% TFA)

Sources & evidence

ORD record
ord-e4ce3127968b47cea49930f0dc5b7d16
Source dataset
uspto-grants-2002_03
Patent number
US06362201B1

Reaction notes

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