Trifluoroacetic acid → N-(2-{5-[4-(Benzothiazol-2-yloxy)-benzyl]-hexahydro-pyrrolo[3,4-b]pyrrol-1-yl}-2-oxo-ethyl)-2,2,2-trifluoro-acetamide

HRID 545619Notes

Reaction equation

HRID 545619 reaction equation
Cl.[NH:2]1[CH2:6][CH2:5][CH:4]2[CH2:7][N:8]([CH2:10][C:11]3[CH:26]=[CH:25][C:14]([O:15][C:16]4[S:17][C:18]5[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=5[N:20]=4)=[CH:13][CH:12]=3)[CH2:9][CH:3]12.CCN(CC)CC.[C:34]([NH:41][CH2:42][C:43]([OH:45])=O)(OC(C)(C)C)=[O:35].Cl.CN(C)CCCN=C=NCC.[F:58][C:59]([F:64])([F:63])C(O)=O>C(Cl)Cl.CO.CS(C)=O>[S:17]1[C:18]2[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=2[N:20]=[C:16]1[O:15][C:14]1[CH:25]=[CH:26][C:11]([CH2:10][N:8]2[CH2:7][CH:4]3[CH:3]([N:2]([C:43](=[O:45])[CH2:42][NH:41][C:34](=[O:35])[C:59]([F:64])([F:63])[F:58])[CH2:6][CH2:5]3)[CH2:9]2)=[CH:12][CH:13]=1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 78288N-(tert-butoxycarbonyl)glycineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 425990812-[4-(Hexahydro-pyrrolo[3,4-b]pyrrol-5-ylmethyl)-phenoxy]-benzothiazole hydrochloride

Product 1

HCID 42599593N-(2-{5-[4-(Benzothiazol-2-yloxy)-benzyl]-hexahydro-pyrrolo[3,4-b]pyrrol-1-yl}-2-oxo-ethyl)-2,2,2-trifluoro-acetamideYield 20%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 22036561Dimethyl sulfoxide methanolSolvent

Procedure

To a stirred solution of 2-[4-(hexahydro-pyrrolo[3,4-b]pyrrol-5-ylmethyl)-phenoxy]-benzothiazole hydrochloride (100 mg, 0.26 mmol) and Et3N (215 μL, 1.6 mmol) in CH2Cl2 (2 mL) was added N-Boc-glycine (95 mg, 0.5 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (104 mg, 0.5 mmol). The resulting solution was then stirred at rt for 16 h. The resulting mixture was then treated with trifluoroacetic acid (1 mL) at rt for 3 h. The crude solid was dissolved in CH3OH/DMSO (2:1) and purified via reverse phase preparative HPLC to yield the title compound as a fluffy white solid (26 mg, 20%). MS (ESI): mass calcd. for C24H23F3N4O3S, 504.5; m/z found, 505.2 [M+H]+. 1H NMR (500 MHz, CDCl3): 7.74 (d, J=7.7 Hz, 1H), 7.68 (d, J=8.0 Hz, 1H), 7.56-7.49 (m, 1H), 7.42-7.26 (m, 6H), 4.55-4.45 (m, 1H), 4.17-3.87 (m, 2H), 3.67 (d, J=13.1 Hz, 1H), 3.60-3.38 (m, 3H), 3.09-2.81 (m, 2H), 2.78-2.54 (m, 2H), 2.52-2.35 (m, 1H), 2.20-2.06 (m, 1H), 2.02-1.87 (m, 1H).

Workup

  1. custompurified via reverse phase preparative HPLC

Sources & evidence

ORD record
ord-4d54b3de7b0f460fbc37950a2a5d8cdd
Source dataset
uspto-grants-2011_05
Patent number
US07935725B2

Reaction notes

Loading…