Diisopropylethylamine → 2-chloro-7-(4-fluorophenyl)-4-((S)-3-fluoropyrrolidin-1-yl)-6,7-dihydro-5H cyclopenta[d]pyrimidine

HRID 2370127Notes

Reaction equation

HRID 2370127 reaction equation
[Cl:1][C:2]1[N:3]=[C:4](Cl)[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.CCN(C(C)C)C(C)C.[F:28][C@H:29]1[CH2:33][CH2:32][NH:31][CH2:30]1>CO>[Cl:1][C:2]1[N:3]=[C:4]([N:31]2[CH2:32][CH2:33][C@H:29]([F:28])[CH2:30]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

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 7016277(S)-3-fluoropyrrolidineHCID 580754242,4-Dichloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[D]pyrimidine

Product 1

HCID 580757872-chloro-7-(4-fluorophenyl)-4-((S)-3-fluoropyrrolidin-1-yl)-6,7-dihydro-5H cyclopenta[d]pyrimidine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 2,4-dichloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine (Preparation H) (135 mg, 0.477 mmol) in MeOH (4768 μL) was added DIPEA (208 μL, 1.192 mmol), then (S)-3-fluoropyrrolidine (46.7 mg, 0.524 mmol). The reaction was allowed to stir at ambient temperature for 2 h. The solvent was removed and the residue applied to Silica gel and eluted with an EtOAc/Hex gradient to afford two diasteriomers (Hp1 and Hp2). Hp1: LC-MS (M+H)+=336.2. 1H NMR (500 MHz, CDCl3) δ ppm 7.06-7.13 (2 H, m), 6.93-7.00 (2 H, m), 5.32 (1 H, td, J=52.57, 3.17 Hz), 4.17 (1 H, dd, J=9.16, 5.49 Hz), 4.06-4.14 (1 H, m), 3.98-4.06 (1 H, m), 3.76-3.90 (2 H, m), 3.25 (1 H, ddd, J=15.11, 8.55, 6.26 Hz), 3.08-3.16 (1 H, m), 2.51-2.60 (1 H, m, J=13.20, 9.12, 9.12, 6.41 Hz), 2.32-2.42 (1 H, m), 2.00-2.17 (2 H, m). Hp2: LC-MS (M+H)+=336.2. 1H NMR (500 MHz, CDCl3) δ ppm 7.06-7.14 (2 H, m), 6.94-7.02 (2 H, m), 5.25-5.40 (1 H, m), 3.99-4.24 (3 H, m), 3.75-3.92 (2 H, m), 3.19-3.28 (1 H, m), 3.10-3.19 (1 H, m), 2.57 (1 H, dddd, J=13.24, 8.74, 8.55, 4.58 Hz), 2.31-2.43 (1 H, m), 1.94-2.17 (2 H, m)

Workup

  1. customThe solvent was removed
  2. washeluted with an EtOAc/Hex gradient
  3. customto afford two diasteriomers (Hp1 and Hp2)

Sources & evidence

ORD record
ord-5950141a34104f5db3d088190fb5cbdf
Source dataset
uspto-grants-2014_04
Patent number
US08710061B2

Reaction notes

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