3-(Trifluoromethyl)aniline → 1-(3-Trifluoromethyl-anilino)-4-[(6-chloro-pyridin-3-yl)-methyl]-3-methylisoquinoline

HRID 49232Notes

Reaction equation

HRID 49232 reaction equation
ClC1C2C(=CC=CC=2)C(CC2C=NC(OC)=CC=2)=C(C)N=1.Cl[C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:26]([CH2:33][C:34]2[CH:35]=[N:36][C:37]([Cl:40])=[CH:38][CH:39]=2)=[C:25]([CH3:41])[N:24]=1.[F:42][C:43]([F:52])([F:51])[C:44]1[CH:45]=[C:46]([CH:48]=[CH:49][CH:50]=1)[NH2:47].Cl.O1CCOCC1>CO>[F:42][C:43]([F:51])([F:52])[C:44]1[CH:45]=[C:46]([CH:48]=[CH:49][CH:50]=1)[NH:47][C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:26]([CH2:33][C:34]2[CH:35]=[N:36][C:37]([Cl:40])=[CH:38][CH:39]=2)=[C:25]([CH3:41])[N:24]=1

Participants

6

Reactant 4

HCID 73753-(Trifluoromethyl)anilineHCID 204431481,4-Dioxane hydrochlorideHCID 20636400HCID 20636400, compoundHCID 20636402HCID 20636402, compound

Product 1

HCID 206363951-(3-Trifluoromethyl-anilino)-4-[(6-chloro-pyridin-3-yl)-methyl]-3-methylisoquinoline

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Analogously to example 36, 0.70 g (2.3 mmol) of 1-chloro-4-[(6-methoxy-pyridin-3-yl)-methyl]-3-methylisoquinoline (contains traces of 1-chloro-4-[(6-chloro-pyridin-3-yl)-methyl]-3-methylisoquinoline as an impurity) in 15 ml of methanol are mixed with 741 mg (4.6 mmol) of 3-trifluoromethyl-aniline and 0.58 ml of 4 N HCl/dioxane and reacted for 18 h at 70° C. Extraction and column chromatography (SiO2, methylene chloride/diethylether 50:1→EtOAc→EtOAc/EtOH 10:1) yield 1-(3-trifluoromethyl-anilino)-4-[(6-chloro-pyridin-3-yl)-methyl]-3-methylisoquinoline 45a (m.p. 137° C.; FAB-MS: (M+H)+=428), followed by 1-(3-trifluoromethyl-anilino)-4-[(6-methoxy-pyridin-3-yl)-methyl]-3-methylisoquinoline 45b (m.p. 136-137° C.; FAB-MS: (M+H)+=424), and finally 1-(3-trifluororethyl-anilino)-4-[(6-hydroxy-pyridin-3-yl)-methyl]-3-methylisoquinoline 45c (m.p. 250-252° C.; FAB-MS: (M+H)+=410). The latter can also be obtained by demethylation (1. Me3Sil/CHCl3, 2. hydrolysis) from the 6-methoxy-pyridine derivative.

Workup

  1. customreacted for 18 h at 70° C
  2. extractionExtraction and column chromatography (SiO2, methylene chloride/diethylether 50:1→EtOAc→EtOAc/EtOH 10:1)

Sources & evidence

ORD record
ord-e681688089774f8ba311e2afb9a05b14
Source dataset
uspto-grants-2004_03
Patent number
US06706731B2

Reaction notes

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