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

HRID 1964104Notes

Reaction equation

HRID 1964104 reaction equation
[CH:1]1([C:6]2[CH:37]=[CH:36][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]([O:27]C(C)(C)C)=[O:26])[C:16]5=[C:15]([CH:32]5[CH2:35][CH2:34][CH2:33]5)[C:14]=4[CH:13]=3)=[CH:8][C:7]=2[C:38]([F:41])([F:40])[F:39])[CH2:5][CH2:4][CH2:3][CH2:2]1.NC(CS)C(O)=O>C(O)(C(F)(F)F)=O>[CH:32]1([C:15]2[C:14]3[CH:13]=[C:12]([O:11][CH2:10][C:9]4[CH:36]=[CH:37][C:6]([CH:1]5[CH2:2][CH2:3][CH2:4][CH2:5]5)=[C:7]([C:38]([F:41])([F:40])[F:39])[CH:8]=4)[CH:20]=[CH:19][C:18]=3[N:17]3[CH2:21][CH2:22][CH:23]([CH2:24][C:25]([OH:27])=[O:26])[C:16]=23)[CH2:35][CH2:34][CH2:33]1

Participants

4

Reactant 2

HCID 594DL-cysteineHCID 86654870tert-Butyl 2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-9-cyclobutyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate

Product 1

HCID 583296092-(9-Cyclobutyl-7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic AcidYield 42.2%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
23 °C

Procedure

tert-Butyl 2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-9-cyclobutyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate (17.2 mg, 0.031 mmol) was added to a solution of 2-amino-3-mercaptopropanoic acid (3.76 mg, 0.031 mmol) in TFA (1 mL) and were stirred at 23° C. for 15 min in a 20 mL sealed scintillation vial. After 15 min, the reaction mixture was poured into about 4 mL of ice water. The product precipitated and was collected by vacuum filtration. The solid was washed with n-hexane (3×5 mL) and dried (vacuum oven) to give the title compound as an off-white solid (6.7 mg). LCMS m/z=512.5 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.53-1.72 (m, 4H), 1.80-1.91 (m, 3H), 1.93-2.04 (m, 3H), 2.17-2.36 (m, 5H), 2.39-2.48 (m, 1H), 2.63 (dd, J=15.98, 3.98 Hz, 1H), 2.69-2.78 (m, 1H), 3.19-3.28 (m, 1H), 3.57-3.69 (m, 2H), 3.90-4.02 (m, 2H), 5.16 (s, 2H), 6.76 (dd, J=8.72, 2.40 Hz, 1H), 7.07 (d, J=2.27 Hz, 1H), 7.14 (d, J=8.72 Hz, 1H), 7.62 (d, J=8.09 Hz, 1H), 7.67-7.76 (m, 2H), 12.26 (bs, 1H).

Workup

  1. customsealed scintillation vial
  2. waitAfter 15 min
  3. customThe product precipitated
  4. filtrationwas collected by vacuum filtration
  5. washThe solid was washed with n-hexane (3×5 mL)
  6. customdried (vacuum oven)

Sources & evidence

ORD record
ord-cf7df66ee3bc4ba38beb9aea789e1789
Source dataset
uspto-grants-2013_04
Patent number
US08415484B2

Reaction notes

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