2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-amine → N-[3-(3-{2-[(2-Amino-2,3-dihydro-1H-inden-5-yl)amino]-4-pyrimidinyl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]-2,6-difluorobenzamide

HRID 1159983Notes

Reaction equation

HRID 1159983 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[C:9]([C:17]3[CH:18]=[C:19]([NH:23][C:24](=[O:33])[C:25]4[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=4[F:32])[CH:20]=[CH:21][CH:22]=3)=[N:10][N:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=23)[CH:5]=[CH:4][N:3]=1.C[N:35]1[CH2:44][CH2:43][C:42]2[C:37](=[CH:38][C:39]([NH2:45])=[CH:40][CH:41]=2)[CH2:36]1>CC(O)C.Cl>[NH2:35][CH:44]1[CH2:36][C:37]2[C:42](=[CH:41][CH:40]=[C:39]([NH:45][C:2]3[N:7]=[C:6]([C:8]4[C:9]([C:17]5[CH:18]=[C:19]([NH:23][C:24](=[O:33])[C:25]6[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=6[F:32])[CH:20]=[CH:21][CH:22]=5)=[N:10][N:11]5[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=45)[CH:5]=[CH:4][N:3]=3)[CH:38]=2)[CH2:43]1

Participants

5

Reactant 2

HCID 129995062-Methyl-1,2,3,4-tetrahydroisoquinolin-7-amineHCID 59513803N-{3-[3-(2-Chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,6-difluorobenzamide

Product 1

HCID 59513754N-[3-(3-{2-[(2-Amino-2,3-dihydro-1H-inden-5-yl)amino]-4-pyrimidinyl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]-2,6-difluorobenzamideYield 60.2%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 3776IsopropanolSolvent

Conditions

Temperature
90 °C

Procedure

To a suspension of N-{3-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,6-difluorobenzamide (100 mg, 0.22 mmol) (prepared according to a procedure similar to that described in Example 27, Step C) and 2-methyl-1,2,3,4-tetrahydro-7-isoquinolinamine (44 mg, 0.27 mmol) in 2-propanol (3 mL) was added 2 drops of concentrated HCl. The mixture was stirred at 90° C. overnight, and the reaction mixture was partitioned between saturated aqueous NaHCO3 and 4:1 CHCl3/MeOH. The organic layer was dried over MgSO4, filtered, and purified by flash chromatography to give the title compound as a yellow oil (76 mg, 59% yield). 1H NMR (400 MHz, d6-DMSO): δ 10.95 (s, 1H), 9.44 (s, 1H), 8.85 (d, J=7.0 Hz, 1H), 8.46 (d, J=9.0 Hz, 1H), 8.26 (d, J=5.3 Hz, 1H), 8.02 (s, 1H), 7.83 (d, J=9.2 Hz, 1H), 7.55-7.65 (m, 1H), 7.45-7.49 (m, 2H), 7.35-7.39 (m, 1H), 7.26 (t, J=8.1 Hz, 2H), 7.14 (t, J=6.8 Hz, 1H), 6.97 (d, J=8.4 Hz, 1H), 6.72 (d, J=8.0 Hz, 1H), 6.52 (d, J=5.3 Hz, 1H), 6.35 (d, J=8.0 Hz, 1H), 6.21 (s, 1H), 3.30 (s, 2H) 2.75 (t, J=5.5 Hz, 2H), 2.52-2.63 (m, 2H), 2.26 (s, 3H). MS (ESI) m/z=588 [M+H]+.

Workup

  1. customprepared
  2. customthe reaction mixture was partitioned between saturated aqueous NaHCO3 and 4:1 CHCl3/MeOH
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. custompurified by flash chromatography

Sources & evidence

ORD record
ord-952c48f84f7d423bb7edee3dcbea3436
Source dataset
uspto-grants-2010_10
Patent number
US07812022B2

Reaction notes

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