1-(2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-3-(trifluoromethyl)pyrrolidin-3-ol → Trifluoroacetic acid

HRID 451159Notes

Reaction equation

HRID 451159 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:18]2[CH2:22][CH2:21][C:20]([C:24]([F:27])([F:26])[F:25])([OH:23])[CH2:19]2)[C:5]2[CH2:10][CH2:9][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:28][C:29]1[N:30]=[CH:31][N:32]([C:34]2[CH:40]=[CH:39][C:37]([NH2:38])=[CH:36][C:35]=2[O:41][CH3:42])[CH:33]=1>>[Cl:28][C:29]1[N:30]=[CH:31][N:32]([C:34]2[CH:40]=[CH:39][C:37]([NH:38][C:2]3[N:3]=[C:4]([N:18]4[CH2:22][CH2:21][C:20]([C:24]([F:26])([F:27])[F:25])([OH:23])[CH2:19]4)[C:5]4[CH2:10][CH2:9][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:36][C:35]=2[O:41][CH3:42])[CH:33]=1.[C:20]([OH:41])([C:24]([F:27])([F:26])[F:25])=[O:23]

Participants

4

Reactant 2

HCID 580756361-(2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-3-(trifluoromethyl)pyrrolidin-3-olHCID 580757574-(4-chloro-1H-imidazol-1-yl)-3-methoxyaniline

Product 2

HCID 6422Trifluoroacetic acidHCID 509142311-(2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenylamino)-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-3-(trifluoromethyl)pyrrolidin-3-ol

Procedure

1-(2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-3-(trifluoromethyl)pyrrolidin-3-ol (Preparation Hi) (245 mg, 0.610 mmol) and 4-(4-chloro-1H-imidazol-1-yl)-3-methoxyaniline (Preparation A) (177 mg, 0.793 mmol) were combined and purified as per Example 16 to give 1-(2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenylamino)-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-3-(trifluoromethyl)pyrrolidin-3-ol, TFA (first to elute, diastereomer A) (51.4 mg, 0.073 mmol) as a clear, colorless glass. LC-MS (M+H)+=589.1. 1H NMR (500 MHz, MeOD) δ ppm 7.97 (1H, s), 7.67 (1H, s), 7.17-7.26 (3H, m), 7.14 (1H, d, J=8.55 Hz), 7.04 (2H, t, J=8.70 Hz), 6.91 (1H, d, J=8.55 Hz), 4.14 (2H, t, J=8.85 Hz), 3.93-4.06 (3H, m), 3.58-3.68 (3H, m), 3.21-3.31 (1H, m), 3.09-3.21 (1H, m), 2.51-2.63 (1H, m), 2.28-2.41 (1H, m), 2.16 (1H, dd, J=12.82, 6.41 Hz), 1.95 (1H, dq, J=12.82, 8.55 Hz). The relative stereochemisty of Example 27 was not determined.

Workup

  1. custompurified as per Example 16

Sources & evidence

ORD record
ord-0b8cd14a197342fbb3332fac656e898c
Source dataset
uspto-grants-2013_07
Patent number
US08486952B2

Reaction notes

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