Water → 2-(7-(3-Cyano-4-isopropoxybenzyloxy)-9-(methylsulfonyl)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic Acid

HRID 515737Notes

Reaction equation

HRID 515737 reaction equation
N[C@H](C(O)=O)CS.[C:8]([C:10]1[CH:11]=[C:12]([CH:39]=[CH:40][C:41]=1[O:42][CH:43]([CH3:45])[CH3:44])[CH2:13][O:14][C:15]1[CH:23]=[CH:22][C:21]2[N:20]3[CH2:24][CH2:25][CH:26]([CH2:27][C:28]([O:30]C(C)(C)C)=[O:29])[C:19]3=[C:18]([S:35]([CH3:38])(=[O:37])=[O:36])[C:17]=2[CH:16]=1)#[N:9].O.C(OCC)(=O)C>C(O)(C(F)(F)F)=O.C(Cl)Cl>[C:8]([C:10]1[CH:11]=[C:12]([CH:39]=[CH:40][C:41]=1[O:42][CH:43]([CH3:45])[CH3:44])[CH2:13][O:14][C:15]1[CH:23]=[CH:22][C:21]2[N:20]3[CH2:24][CH2:25][CH:26]([CH2:27][C:28]([OH:30])=[O:29])[C:19]3=[C:18]([S:35]([CH3:38])(=[O:37])=[O:36])[C:17]=2[CH:16]=1)#[N:9]

Participants

7

Reactant 4

HCID 962WaterHCID 5862L-(+)-CysteineHCID 8857Ethyl AcetateHCID 67250041tert-Butyl 2-(7-(3-Cyano-4-isopropoxybenzyloxy)-9-(methylsulfonyl)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate

Product 1

HCID 583296202-(7-(3-Cyano-4-isopropoxybenzyloxy)-9-(methylsulfonyl)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic Acid

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
0 °C

Procedure

D/L-Cysteine (40.5 mg, 0.334 mmol) was dissolved in TFA (1 mL) and cooled down to 0° C. The solution was added to a solution of tert-butyl 2-(7-(3-cyano-4-isopropoxybenzyloxy)-9-(methylsulfonyl)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate (36 mg, 0.067 mmol) in DCM (1 mL) at 0° C. The reaction was stirred at this temperature for 1 h. Water was added, then ethyl acetate was added. The organic layer was separated, washed with water and brine, dried over anhydrous Na2SO4, and concentrated. The residue was purified by preparative HPLC. The combined fractions were partially concentrated in vacuo and diluted with ethyl acetate. The organic layer was separated, washed with water, and dried over anhydrous Na2SO4. The solvent was evaporated to give the title compound as white solid. LCMS m/z=483.3 [M+H]+; 1H NMR (400 MHz, CDCl3) δ ppm 1.41 (d, J=6.0 Hz, 6H), 2.46-2.55 (m, 1H), 2.84 (dd, J=16.7 and 9.5 Hz, 1H), 2.92-3.03 (m, 1H), 3.11 (s, 3H), 3.33 (dd, J=16.7, 3.4 Hz, 1H), 3.98-4.08 (m, 1H), 4.10-4.17 (m, 1H), 4.17-4.25 (m, 1H), 4.62-4.69 (m, 1H), 5.04 (s, 2H), 6.95-7.00 (m, 2H), 7.22 (d, J=8.8 Hz, 1H), 7.41 (d, J=2.4 Hz, 1H), 7.59 (dd, J=8.7, 2.2 Hz, 1H), 7.66 (d, J=2.2 Hz, 1H).

Workup

  1. customThe organic layer was separated
  2. washwashed with water and brine
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by preparative HPLC
  6. concentrationThe combined fractions were partially concentrated in vacuo
  7. additiondiluted with ethyl acetate
  8. customThe organic layer was separated
  9. washwashed with water
  10. dry with materialdried over anhydrous Na2SO4
  11. customThe solvent was evaporated

Sources & evidence

ORD record
ord-f0cf2451e90f42c292f6b4054d18a0a4
Source dataset
uspto-grants-2015_08
Patent number
US09108969B2

Reaction notes

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