4-(4-chloro-1H-imidazol-1-yl)-3-methoxyaniline → N2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-7-(4-fluorophenyl)-N4-methyl-5,7-dihydrofuro[3,4-d]pyrimidine-2,4-diamine

HRID 451168Notes

Reaction equation

HRID 451168 reaction equation
Cl[C:2]1[N:3]=[C:4]([NH:18][CH3:19])[C:5]2[CH2:10][O:9][CH:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:6]=2[N:7]=1.[Cl:20][C:21]1[N:22]=[CH:23][N:24]([C:26]2[CH:32]=[CH:31][C:29]([NH2:30])=[CH:28][C:27]=2[O:33][CH3:34])[CH:25]=1>>[Cl:20][C:21]1[N:22]=[CH:23][N:24]([C:26]2[CH:32]=[CH:31][C:29]([NH:30][C:2]3[N:3]=[C:4]([NH:18][CH3:19])[C:5]4[CH2:10][O:9][CH:8]([C:11]5[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=5)[C:6]=4[N:7]=3)=[CH:28][C:27]=2[O:33][CH3:34])[CH:25]=1

Participants

3

Reactant 2

HCID 580757574-(4-chloro-1H-imidazol-1-yl)-3-methoxyanilineHCID 580757952-chloro-7-(4-fluorophenyl)-N-methyl-5,7-dihydrofuro[3,4-d]pyrimidin-4-amine

Product 1

HCID 58075428N2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-7-(4-fluorophenyl)-N4-methyl-5,7-dihydrofuro[3,4-d]pyrimidine-2,4-diamine

Procedure

2-chloro-7-(4-fluorophenyl)-N-methyl-5,7-dihydrofuro[3,4-d]pyrimidin-4-amine (Preparation Ma) (149 mg, 0.533 mmol) and 4-(4-chloro-1H-imidazol-1-yl)-3-methoxyaniline (Preparation A) (119 mg, 0.533 mmol) were combined and purified as per Example 75 to give the racemate N2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-7-(4-fluorophenyl)-N4-methyl-5,7-dihydrofuro[3,4-d]pyrimidine-2,4-diamine which was separated by multiple chiral SFC injections (OJ-H 30×250 mm, 5 μM, 35% MeOH (0.1% DEA)/CO2) to give N2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-7-(4-fluorophenyl)-N4-methyl-5,7-dihydrofuro[3,4-d]pyrimidine-2,4-diamine (first to elute, enantiomer A) (18.3 mg, 0.039 mmol, 7.36% yield) as a white scrapable foam. LC-MS (M+H)+=467.0. 1H NMR (500 MHz, MeOD) δ ppm 7.89-7.94 (1H, m), 7.65-7.69 (1H, m), 7.36-7.42 (2H, m), 7.20-7.24 (1H, m), 7.13-7.18 (1H, m), 7.03-7.12 (3H, m), 5.79 (1H, br. s.), 5.08-5.16 (1H, m), 4.95-5.03 (1H, m), 3.68-3.73 (3H, m), 3.02-3.07 (3H, m). The absolute stereochemistry of Example 79A was not determined.

Workup

  1. custompurified as per Example 75

Sources & evidence

ORD record
ord-6eeea908495247e9b8b7a43f860b2c20
Source dataset
uspto-grants-2013_07
Patent number
US08486952B2

Reaction notes

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