4,6-Dichloropyrimidine → HCID 86659170, compound

HRID 2367234Notes

Reaction equation

HRID 2367234 reaction equation
[CH:1]1([NH:7][C:8]([C@H:10]2[CH2:15][CH2:14][C@@H:13]([C:16]([F:19])([F:18])[F:17])[NH:12][CH2:11]2)=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Cl:30][C:31]1[CH:36]=[C:35](Cl)[N:34]=[C:33]([S:38][CH3:39])[N:32]=1.ClC1N=CN=C(Cl)C=1>C1COCC1>[Cl:30][C:31]1[N:32]=[C:33]([S:38][CH3:39])[N:34]=[C:35]([N:12]2[C@H:13]([C:16]([F:19])([F:17])[F:18])[CH2:14][CH2:15][C@H:10]([C:8]([NH:7][CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]3)=[O:9])[CH2:11]2)[CH:36]=1

Participants

6

Reactant 4

HCID 709434,6-DichloropyrimidineHCID 805314,6-Dichloro-2-(methylthio)pyrimidineHCID 2733832Lithium HexamethyldisilazideHCID 66990530HCID 66990530, compound

Product 1

HCID 86659170HCID 86659170, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To cis-N-cyclohexyl-6-(trifluoromethyl)-3-piperidinecarboxamide (1.0 g, 3.2 mmol) in THF (15 mL) was added 1M LiHMDS in THF (11 mL, 11.00 mmol) at room temperature. After 5 minutes, 4,6-dichloro-2-(methylthio)pyrimidine (0.620 g, 3.18 mmol) was added. After 10 minutes, LCMS analysis of the reaction mixture indicated the presense of ˜85% desired product+13% of dichloropyrimidine SM. The reaction mixture was poured onto saturated NH4Cl and EtOAc. The organic layer was separated, washed with brine, dried (MgSO4), filtered and concentrated. A solid cartridge was prepared by adding EtOAc (˜200 mL) to the crude and SiO2 (3 g). The mixture was concentrated. Flash chromatography (100% Hexanes to 50% EtOAc in Hexanes, then 100% EtOAc) afforded the title compound (690 mg) as an off-white solid. LC-MS (ES) m/z=437, 439 [M+H]+.

Workup

  1. waitAfter 10 minutes

Sources & evidence

ORD record
ord-b732c079e220447baa23ff417f1ebb8e
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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