2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-amine → N-[3-(4-fluoro-3-{2-[(2-methyl-1,2,3,4-tetrahydro-7-isoquinolinyl)amino]-4-pyrimidinyl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]-2-(2-thienyl)acetamide

HRID 1157572Notes

Reaction equation

HRID 1157572 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[C:9]([C:18]3[CH:19]=[C:20]([NH:24][C:25](=[O:32])[CH2:26][C:27]4[S:28][CH:29]=[CH:30][CH:31]=4)[CH:21]=[CH:22][CH:23]=3)=[N:10][N:11]3[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[C:12]=23)[CH:5]=[CH:4][N:3]=1.[CH3:33][N:34]1[CH2:43][CH2:42][C:41]2[C:36](=[CH:37][C:38]([NH2:44])=[CH:39][CH:40]=2)[CH2:35]1>CC(O)C.Cl>[F:17][C:13]1[C:12]2[N:11]([N:10]=[C:9]([C:18]3[CH:19]=[C:20]([NH:24][C:25](=[O:32])[CH2:26][C:27]4[S:28][CH:29]=[CH:30][CH:31]=4)[CH:21]=[CH:22][CH:23]=3)[C:8]=2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:44][C:38]3[CH:37]=[C:36]4[C:41]([CH2:42][CH2:43][N:34]([CH3:33])[CH2:35]4)=[CH:40][CH:39]=3)[N:7]=2)[CH:16]=[CH:15][CH:14]=1

Participants

5

Reactant 2

HCID 129995062-Methyl-1,2,3,4-tetrahydroisoquinolin-7-amineHCID 57737169N-{3-[3-(2-chloro-4-pyrimidinyl)-4-fluoropyrazolo[1,5-a]pyridin-2-yl]phenyl}-2-(2-thienyl)acetamide

Product 1

HCID 57737245N-[3-(4-fluoro-3-{2-[(2-methyl-1,2,3,4-tetrahydro-7-isoquinolinyl)amino]-4-pyrimidinyl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]-2-(2-thienyl)acetamideYield 60%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 3776IsopropanolSolvent

Procedure

To the solution of N-{3-[3-(2-chloro-4-pyrimidinyl)-4-fluoropyrazolo[1,5-a]pyridin-2-yl]phenyl}-2-(2-thienyl)acetamide (0.080 g) in i-PrOH (5 mL) was added 2-methyl-1,2,3,4-tetrahydro-7-isoquinolinamine (0.041 g) and 2 drops of concentrate hydrochloric acid. The reaction was microwaved in a sealed tube at 180° C. for 10 min. The i-PrOH was removed by rotary evaporation and the residue was treated with sat. NaHCO3 (5 mL), extracted with EtOAc (2×5 mL), and dried (Na2SO4). Concentration and purification with column chromatography afforded the title compound as a white solid (0.060 g, 60% yield). 1H NMR (400 MHz, DMSO-d6) δ 2.25 (s, 3H), 2.63 (s, 2H), 3.17 (s, 2H), 3.84 (s, 2H), 6.80 (s, 1H), 6.89 (dd, 1H, J=4.94, 3.11 Hz), 6.95 (d, 2H, J=3.66 Hz), 6.99-7.05 (m, 1H), 7.08 (d, 1H, J=7.68 Hz), 7.18 (s, 1H), 7.24-7.30 (m, 2H), 7.35-7.37 (m, 1H), 7.58 (d, 1H, J=1.10 Hz), 8.05 (t, 1H, J=1.83 Hz), 8.44 (d, 1H, J=5.12 Hz), 8.72 (d, 1H, J=6.95 Hz), 9.39 (s, 1H), 10.32 (s, 1H). ES-LC/MS m/z=590 [M+H]+.

Workup

  1. customThe reaction was microwaved in a sealed tube at 180° C. for 10 min
  2. customThe i-PrOH was removed by rotary evaporation
  3. additionthe residue was treated with sat. NaHCO3 (5 mL)
  4. extractionextracted with EtOAc (2×5 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationConcentration and purification with column chromatography

Sources & evidence

ORD record
ord-62b289ff46464e808a52402199b07f5e
Source dataset
uspto-grants-2010_10
Patent number
US07807673B2

Reaction notes

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