Trifluoroacetic acid → 6-({3-[4-(1,3-Thiazol-2-ylcarbonyl)piperazin-1-yl]azetidin-1-yl}carbonyl)-1,2,3,4-tetrahydroisoquinoline

HRID 2365618Notes

Reaction equation

HRID 2365618 reaction equation
C(OC([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:18]([N:20]3[CH2:23][CH:22]([N:24]4[CH2:29][CH2:28][N:27]([C:30]([C:32]5[S:33][CH:34]=[CH:35][N:36]=5)=[O:31])[CH2:26][CH2:25]4)[CH2:21]3)=[O:19])[CH:14]=2)[CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[S:33]1[CH:34]=[CH:35][N:36]=[C:32]1[C:30]([N:27]1[CH2:28][CH2:29][N:24]([CH:22]2[CH2:23][N:20]([C:18]([C:13]3[CH:14]=[C:15]4[C:10](=[CH:11][CH:12]=3)[CH2:9][NH:8][CH2:17][CH2:16]4)=[O:19])[CH2:21]2)[CH2:25][CH2:26]1)=[O:31]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59625727HCID 59625727, compound

Product 1

HCID 596257876-({3-[4-(1,3-Thiazol-2-ylcarbonyl)piperazin-1-yl]azetidin-1-yl}carbonyl)-1,2,3,4-tetrahydroisoquinolineYield 101.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of compound 17c (826 mg, 1.61 mmol) in CH2Cl2 (5 mL) was added trifluoroacetic acid (1 mL) at room temperature. The mixture was stirred at room temperature for 18 h. The mixture was extracted with CH2Cl2, and H2O after basifying the water layer to pH˜8 with 1N aqueous NaOH. The organic solution was dried over Na2SO4 and concentrated. Purification of the residue by flash column chromatography (silica gel, 2% MeOH/EtOAc) gave Cpd 916 (675 mg). 1H NMR (400 MHz, CDCl3): δ 7.88 (d, J=3.3 Hz, 1H), 7.55 (d, J=3.3 Hz, 1H), 7.41 (s, 1H), 7.37 (d, J=8.03 Hz, 1H), 7.05 (d, J=8.3 Hz, 1H), 4.54 (br. s., 1H), 4.44 (br. s., 1H), 4.01-4.35 (m, 6H), 3.75-3.95 (m, 2H), 3.12-3.31 (m, 2H), 2.85 (t, J=5.8 Hz, 1H), 2.49 (br. s., 4H). MS m/z (M+H+) 412.0.

Workup

  1. extractionThe mixture was extracted with CH2Cl2, and H2O
  2. dry with materialThe organic solution was dried over Na2SO4
  3. concentrationconcentrated
  4. customPurification of the residue by flash column chromatography (silica gel, 2% MeOH/EtOAc)

Sources & evidence

ORD record
ord-eb3d75a2c7ed4b139032f8d3c373d323
Source dataset
uspto-grants-2014_04
Patent number
US08697683B2

Reaction notes

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