Trifluoroacetic acid → (+/-)-cis-n-(5-(Isoquinolin-6-yl)-1,3,4-thiadiazol-2-yl)-3-phenylpyrrolidine-2-carboxamide

HRID 2075346Notes

Reaction equation

HRID 2075346 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3[S:15][C:14]([NH:16][C:17]([C@H:19]4[C@@H:23]([C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=5)[CH2:22][CH2:21][N:20]4C(OC(C)(C)C)=O)=[O:18])=[N:13][N:12]=3)=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3[S:15][C:14]([NH:16][C:17]([C@H:19]4[C@@H:23]([C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=5)[CH2:22][CH2:21][NH:20]4)=[O:18])=[N:13][N:12]=3)=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57991961HCID 57991961, compound

Product 1

HCID 57991867(+/-)-cis-n-(5-(Isoquinolin-6-yl)-1,3,4-thiadiazol-2-yl)-3-phenylpyrrolidine-2-carboxamideYield 7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred mixture of (±)-cis-tert-butyl 2-((5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-yl)carbamoyl)-3-phenylpyrrolidine-1-carboxylate (54 mg, 0.11 mmol) in DCM (3.0 mL) was added TFA (3.0 mL). The mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated. The crude residue was purified by flash column chromatography (eluting with a gradient of DCM to DCM containing 5% of 10% MeOH in ammonia) to provide (±)-cis-N-(5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-yl)-3-phenylpyrrolidine-2-carboxamide as a white solid (3.0 mg, 7%). LCMS (M+H) 402.2 calc. for C22H20N5OS 402.1. 1H NMR (400 MHz, CDCl3): δ ppm 9.23 (s, 1H) 8.55 (d, J=4.89 Hz, 1H) 8.08-8.29 (m, 2H) 7.97 (d, J=7.63 Hz, 1H) 7.65 (d, J=5.48 Hz, 1H) 7.15-7.24 (m, 5H) 4.42-4.87 (m, 1H) 3.89 (d, J=5.48 Hz, 1H) 3.56-3.72 (m, 1H) 3.35-3.51 (m, 1H) 2.18-2.54 (m, 2H). 2H obscured.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customThe crude residue was purified by flash column chromatography (
  3. washeluting with a gradient of DCM to DCM containing 5% of 10% MeOH in ammonia)

Sources & evidence

ORD record
ord-9ec142968c294be1a1e994e575ac3303
Source dataset
uspto-grants-2011_04
Patent number
US07919504B2

Reaction notes

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