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

HRID 1159998Notes

Reaction equation

HRID 1159998 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:29])[C:25]([F:28])([F:27])[F:26])[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.[CH3:30][N:31]1[CH2:40][CH2:39][C:38]2[C:33](=[CH:34][C:35]([NH2:41])=[CH:36][CH:37]=2)[CH2:32]1>CC(O)C.Cl>[F:26][C:25]([F:28])([F:27])[C:24]([NH:23][C:19]1[CH:20]=[CH:21][CH:22]=[C:17]([C:9]2[C:8]([C:6]3[CH:5]=[CH:4][N:3]=[C:2]([NH:41][C:35]4[CH:34]=[C:33]5[C:38]([CH2:39][CH2:40][N:31]([CH3:30])[CH2:32]5)=[CH:37][CH:36]=4)[N:7]=3)=[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][N:11]3[N:10]=2)[CH:18]=1)=[O:29]

Participants

5

Reactant 2

HCID 129995062-Methyl-1,2,3,4-tetrahydroisoquinolin-7-amineHCID 59513717N-{3-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,2,2-trifluoroacetamide

Product 1

HCID 595137262,2,2-Trifluoro-N-[3-(3-{2-[(2-methyl-1,2,3,4-tetrahydro-7-isoquinolinyl)amino]-4-pyrimidinyl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]acetamideYield 72%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

To a suspension of N-{3-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,2,2-trifluoroacetamide (310 mg, 0.74 mmol, which may be prepared according to Example 11, Step C) and 2-methyl-1,2,3,4-tetrahydro-7-isoquinolinamine (150 mg, 0.92 mmol) in 2-propanol (10 mL) was added 6 drops concentrated HCl. The reaction was stirred for 18 h at 80° C., then partitioned between saturated aqueous NaHCO3 and 20% (v/v) MeOH in EtOAc. The aqueous layer was extracted with 20% (v/v) MeOH in EtOAc, and the combined organic layers were dried over Na2SO4, filtered, and adsorbed onto silica. The crude product was purified by column chromatography to generate the title compound in 72% yield (290 mg, 0.53 mmol). 1H NMR (400 MHz, d6-DMSO) δ 11.39 (s, 1H), 9.45 (s, 1H), 8.85 (d, J=7.0 Hz, 1H), 8.44 (d, J=8.6 Hz, 1H), 8.27 (d, J=5.1 Hz, 1H), 8.02 (s, 1H), 7.83 (d, J=8.6 Hz, 1H), 7.44-7.55 (m, 4H), 7.38 (d, J=8.2 Hz, 1H), 7.14 (t, J=6.9 Hz, 1H), 6.97 (d, J=8.4 Hz, 1H), 6.50 (d, J=5.3 Hz, 1H), 3.39 (s, 2H), 2.75 (t, J=5.7 Hz, 2H), 2.59 (t, J=5.7 Hz, 2H), 2.32 (s, 3H). MS (ESI) m/z=544 [M+H]+.

Workup

  1. custompartitioned between saturated aqueous NaHCO3 and 20% (v/v) MeOH in EtOAc
  2. extractionThe aqueous layer was extracted with 20% (v/v) MeOH in EtOAc
  3. dry with materialthe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-d4b0aff78d3f45dc98d09947a6660f48
Source dataset
uspto-grants-2010_10
Patent number
US07812022B2

Reaction notes

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