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

HRID 1852599Notes

Reaction equation

HRID 1852599 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 596257276-{3-[4-(Thiazole-2-carbonyl)-piperazin-1-yl]-azetidine-1-carbonyl}-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

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=3.3Hz, 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-0c9c80a78a6942efb4e1a14610e5f6ef
Source dataset
uspto-grants-2015_02
Patent number
US08962607B2

Reaction notes

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