Trifluoroacetic acid → 6-[8-(4-Morpholin-4-yl-phenylamino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl]-3,4-dihydro-2H-isoquinolin-1-one

HRID 1783939Notes

Reaction equation

HRID 1783939 reaction equation
C(OC(=O)[N:7]([C:28]1[CH:33]=[CH:32][C:31]([N:34]2[CH2:39][CH2:38][O:37][CH2:36][CH2:35]2)=[CH:30][CH:29]=1)[C:8]1[C:9]2[N:10]([N:25]=[CH:26][N:27]=2)[C:11]([C:14]2[CH:15]=[C:16]3[C:21](=[CH:22][CH:23]=2)[C:20](=[O:24])[NH:19][CH2:18][CH2:17]3)=[CH:12][N:13]=1)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[N:34]1([C:31]2[CH:30]=[CH:29][C:28]([NH:7][C:8]3[C:9]4[N:10]([N:25]=[CH:26][N:27]=4)[C:11]([C:14]4[CH:15]=[C:16]5[C:21](=[CH:22][CH:23]=4)[C:20](=[O:24])[NH:19][CH2:18][CH2:17]5)=[CH:12][N:13]=3)=[CH:33][CH:32]=2)[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67047378(4-Morpholin-4-yl-phenyl)-[5-(1-oxo-1,2,3,4-tetrahydro-isoquinolin-6-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-yl]-carbamic acid tert-butyl ester

Product 1

HCID 248891206-[8-(4-Morpholin-4-yl-phenylamino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl]-3,4-dihydro-2H-isoquinolin-1-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneCatalyst

Procedure

A solution of (4-morpholin-4-yl-phenyl)-[5-(1-oxo-1,2,3,4-tetrahydro-isoquinolin-6-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-yl]-carbamic acid tert-butyl ester (30 mg, 0.055 mmol) in a 1:1 mixture of TFA:DCM (1 drop of H2O), is stirred at room temperature for 2 hours. The solvent is removed in vacuo and the residue partitioned between ethyl acetate and sat. NaHCO3 (aq). The water layer is extracted with ethyl acetate (2×). The organic layers are combined and evaporated to afford a residue purified by silica gel column chromatography eluting with ethyl acetate. The title compound is isolated (18 mg, 75%) and converted into the mesylate salt (16.6 mg, 97%) using 0.1M methanesulfonic acid (0.317 mL) in MeOH. 1H-NMR (400 MHz, d6-DMSO) δ(ppm) 2.36 (3H, s MsOH), 3.04 (2H, t), 3.21 (4H, m), 3.47 (2H, t), 3.83 (4H, m), 7.11 (2H, d), 7.95-8.02 (6H, m), 8.05 (1H, s), 8.74 (1H, s), 10.09 (1H, br s). LCMS: Rt 2.81 min (97.9%), m/z (APCI) 442 (M+H)+.

Workup

  1. customThe solvent is removed in vacuo
  2. customthe residue partitioned between ethyl acetate and sat. NaHCO3 (aq)
  3. extractionThe water layer is extracted with ethyl acetate (2×)
  4. customevaporated
  5. customto afford a residue
  6. custompurified by silica gel column chromatography
  7. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-7938c3edbdc54f608874a20b6cd31716
Source dataset
uspto-grants-2009_03
Patent number
US07501411B2

Reaction notes

Loading…