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

HRID 1964102Notes

Reaction equation

HRID 1964102 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 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-dec845604b7143a49267b1db0c4781b7
Source dataset
uspto-grants-2013_04
Patent number
US08415484B2

Reaction notes

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