Trifluoroacetic acid → Trifluoroacetic acid

HRID 451162Notes

Reaction equation

HRID 451162 reaction equation
[Cl:1][C:2]1[N:3]=[CH:4][N:5]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]3[N:15]=[C:16]([N:30]4[CH2:35][CH2:34][N:33](C(OC(C)(C)C)=O)[CH2:32][CH2:31]4)[C:17]4[CH2:22][CH2:21][CH:20]([C:23]5[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=5)[C:18]=4[N:19]=3)=[CH:9][C:8]=2[O:43][CH3:44])[CH:6]=1.[C:45]([OH:51])([C:47]([F:50])([F:49])[F:48])=[O:46]>C(Cl)Cl>[Cl:1][C:2]1[N:3]=[CH:4][N:5]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]3[N:15]=[C:16]([N:30]4[CH2:31][CH2:32][NH:33][CH2:34][CH2:35]4)[C:17]4[CH2:22][CH2:21][CH:20]([C:23]5[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=5)[C:18]=4[N:19]=3)=[CH:9][C:8]=2[O:43][CH3:44])[CH:6]=1.[C:45]([OH:51])([C:47]([F:50])([F:49])[F:48])=[O:46]

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 58075688HCID 58075688, compound2×

Product 2

HCID 6422Trifluoroacetic acidYield 23%HCID 66709099HCID 66709099, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 4-(2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenylamino)-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate (Intermediate 31-1) (167 mg, 0.270 mmol) in DCM (5 mL) was added TFA (500 μL, 6.49 mmol). The reaction mixture was stirred at RT for 1 h. The mixture was then concentrated in vacuo. Purification by prep HPLC (Waters Sunfire C18, 50×250 mm, MeOH/H2O/TFA) gave N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-7-(4-fluorophenyl)-4-(piperazin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-amine, TFA (39 mg, 0.062 mmol, 22.78% yield) as a brown oil. LC-MS (M+H)+=520.3. 1H NMR (500 MHz, MeOD) δ ppm 7.83 (1H, br. s.), 7.28-7.46 (5H, m), 7.08-7.21 (3H, m), 4.41-4.53 (1H, m), 4.18-4.28 (4H, m), 3.80 (3H, s), 3.44 (5H, d, J=4.27 Hz), 3.24-3.31 (1H, m), 3.12-3.23 (1H, m), 2.69-2.82 (1H, m), 2.06-2.22 (1H, m).

Workup

  1. concentrationThe mixture was then concentrated in vacuo
  2. customPurification by prep HPLC (Waters Sunfire C18, 50×250 mm, MeOH/H2O/TFA)

Sources & evidence

ORD record
ord-6413e264f61f4534a0da64db58bb769f
Source dataset
uspto-grants-2013_07
Patent number
US08486952B2

Reaction notes

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