Diisopropylethylamine → (1S,4S)-5-(2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-2-oxa-5-azabicyclo[2.2.1]heptane

HRID 2370116Notes

Reaction equation

HRID 2370116 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.Cl.[C@H:20]12[CH2:26][C@H:23]([NH:24][CH2:25]1)[CH2:22][O:21]2.CCN(C(C)C)C(C)C>CO>[Cl:1][C:2]1[N:3]=[C:4]([N:24]2[CH2:25][C@@H:20]3[CH2:26][C@H:23]2[CH2:22][O:21]3)[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 21303398(1S,4S)-2-oxa-5-azabicyclo(2.2.1)heptane hydrochlorideHCID 580754242,4-Dichloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[D]pyrimidine

Product 1

HCID 58075773(1S,4S)-5-(2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-2-oxa-5-azabicyclo[2.2.1]heptaneYield 60.6%

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) (200 mg, 0.706 mmol) in MeOH (7064 μL) was added (1S,4S)-2-Oxa-5-azabicyclo[2.2.1]heptane monohydrochloride (115 mg, 0.848 mmol) and DIPEA (271 μL, 1.554 mmol). The resulting mixture was stirred at RT overnight. The reaction mixture was then concentrated in vacuo. The resulting oil was purified by flash chromatography (Silica, EtOAc/Hexanes) to give (1S,4S)-5-(2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-2-oxa-5-azabicyclo[2.2.1]heptane (148 mg, 0.428 mmol, 60.6% yield). LC-MS (M+H)+=346.1. 1H NMR (500 MHz, MeOD) δ ppm 7.12-7.21 (2 H, m), 7.00-7.08 (2 H, m), 5.11-5.21 (1 H, m), 4.69-4.74 (1 H, m), 4.15-4.26 (1 H, m), 3.88-3.94 (2 H, m), 3.68-3.86 (2 H, m), 3.11-3.21 (1 H, m), 2.56-2.69 (1 H, m), 1.92-2.11 (2 H, m), 1.24-1.42 (2 H, m).

Workup

  1. concentrationThe reaction mixture was then concentrated in vacuo
  2. customThe resulting oil was purified by flash chromatography (Silica, EtOAc/Hexanes)

Sources & evidence

ORD record
ord-780d056c4f2f47d8a6d85a5a22536263
Source dataset
uspto-grants-2014_04
Patent number
US08710061B2

Reaction notes

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