Chlorosuccinimide → 2-(9-Chloro-7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic Acid

HRID 515670Notes

Reaction equation

HRID 515670 reaction equation
[CH:1]1([C:6]2[CH:29]=[CH:28][C:9]([CH2:10][O:11][C:12]3[CH:20]=[CH:19][C:18]4[N:17]5[CH2:21][CH2:22][CH:23]([CH2:24][C:25]([OH:27])=[O:26])[C:16]5=[CH:15][C:14]=4[CH:13]=3)=[CH:8][C:7]=2[C:30]([F:33])([F:32])[F:31])[CH2:5][CH2:4][CH2:3][CH2:2]1.C1C(=O)N([Cl:41])C(=O)C1>C(Cl)Cl>[Cl:41][C:15]1[C:14]2[CH:13]=[C:12]([O:11][CH2:10][C:9]3[CH:28]=[CH:29][C:6]([CH:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)=[C:7]([C:30]([F:33])([F:31])[F:32])[CH:8]=3)[CH:20]=[CH:19][C:18]=2[N:17]2[CH2:21][CH2:22][CH:23]([CH2:24][C:25]([OH:27])=[O:26])[C:16]=12

Participants

4

Reactant 2

HCID 31398ChlorosuccinimideHCID 461749052-(7-(4-Cyclopentyl-3-(trifluoromethyl)benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic Acid

Product 1

HCID 583296182-(9-Chloro-7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic AcidYield 87.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic acid (34 mg, 0.074 mmol) dissolved in DCM (0.500 mL) and cooled to 0° C. was added NCS (9.92 mg, 0.074 mmol). The reaction was stirred at 0° C. for 15 min in a 20 mL sealed scintillation vial. After 15 min, the reaction mixture was diluted with DCM and washed with water (2×10 mL), washed with sodium thiolsulfate pentahydrate (aq.) (2×10 mL), dried over MgSO4 and filtered. The filtrate was concentrated under reduced pressure to give the title compound as a light yellow solid (32 mg). LCMS m/z=492.3 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.54-1.73 (m, 4H), 1.80-1.89 (m, 2H), 1.95-2.05 (m, 2H), 2.24-2.35 (m, 1H), 2.52-2.58 (m, 1H), 2.77-2.87 (m, 1H), 2.94 (dd, J=16.36, 4.11 Hz, 1H), 3.21-3.29 (m, 1H), 3.64-3.72 (m, 1H), 3.95-4.05 (m, 1H), 4.11-4.19 (m, 1H), 5.18 (s, 2H), 6.87 (dd, J=8.78, 2.46 Hz, 1H), 6.98 (d, J=2.27 Hz, 1H), 7.29 (d, J=8.84 Hz, 1H), 7.63 (d, J=7.96 Hz 1H), 7.69-7.76 (m, 2H), 12.35 (bs, 1H).

Workup

  1. customsealed scintillation vial
  2. waitAfter 15 min
  3. washwashed with water (2×10 mL)
  4. washwashed with sodium thiolsulfate pentahydrate (aq.) (2×10 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-6e5588f444a0489c9c42df6d84572e8e
Source dataset
uspto-grants-2015_08
Patent number
US09108969B2

Reaction notes

Loading…