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

HRID 515684Notes

Reaction equation

HRID 515684 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:24]=[CH:25][C:26]=1[O:27][CH:28]([CH3:30])[CH3:29])[CH2:6][O:7][C:8]1[CH:16]=[CH:15][C:14]2[N:13]3[CH2:17][CH2:18][CH:19]([CH2:20][C:21]([OH:23])=[O:22])[C:12]3=[CH:11][C:10]=2[CH:9]=1)#[N:2].C1C(=O)N([Cl:38])C(=O)C1>C(Cl)Cl>[Cl:38][C:11]1[C:10]2[CH:9]=[C:8]([O:7][CH2:6][C:5]3[CH:24]=[CH:25][C:26]([O:27][CH:28]([CH3:30])[CH3:29])=[C:3]([C:1]#[N:2])[CH:4]=3)[CH:16]=[CH:15][C:14]=2[N:13]2[CH2:17][CH2:18][CH:19]([CH2:20][C:21]([OH:23])=[O:22])[C:12]=12

Participants

4

Reactant 2

HCID 31398ChlorosuccinimideHCID 672491622-(7-(3-Cyano-4-isopropoxybenzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic Acid

Product 1

HCID 583295802-(9-Chloro-7-(3-cyano-4-isopropoxybenzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic Acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of the 1St enantiomer obtained during the resolution of Compound 6 by chiral HPLC (described as the enantiomer isolated and having the retention time of 6.7 min per the conditions reported in Example 1.2) (20 mg, 0.049 mmol) in DCM (0.500 mL) was cooled to 0° C. NCS (6.60 mg, 0.049 mmol) was added and the reaction was allowed to continue 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), then washed with sodium thiosulfate pentahydrate (aq) (2×10 mL), dried over MgSO4 and filtered by vacuum filtration. The filtrate was concentrated under reduced pressure to give an enantiomer of Compound 8 as a yellow solid (16.7 mg). LCMS m/z=439.8 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.32 (d, J=5.94 Hz, 6H), 2.25-2.34 (m, 1H), 2.52-2.58 (m, 1H), 2.77-2.87 (m, 1H), 2.94 (dd, J=16.29, 4.17 Hz, 1H), 3.63-3.73 (m, 1H), 3.96-4.04 (m, 1H), 4.12-4.19 (m, 1H), 4.76-4.83 (m, 1H), 5.07 (s, 2H), 6.86 (dd, J=8.84, 2.40 Hz, 1H), 6.96 (d, J=2.40 Hz, 1H), 7.28 (d, J=3.66 Hz, 1H), 7.30 (d, J=3.66 Hz, 1H), 7.72 (dd, J=8.72, 2.27 Hz, 1H), 7.79 (d, J=2.15 Hz, 1H), 12.32 (bs, 1H).

Workup

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

Sources & evidence

ORD record
ord-c54fa4c25043430eaf69d33688e6e103
Source dataset
uspto-grants-2015_08
Patent number
US09108969B2

Reaction notes

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