Methylamine → HCID 71656889, compound

HRID 2278175Notes

Reaction equation

HRID 2278175 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:27]2[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=2)[N:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][CH:18]([C:23](OC)=[O:24])[C:19]([F:22])([F:21])[F:20])=[O:16])[CH2:11][CH2:10]2)=[CH:4][CH:3]=1.[CH3:34][NH2:35]>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:27]2[CH:28]=[CH:29][C:30]([Cl:33])=[CH:31][CH:32]=2)[N:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][CH:18]([C:23]([NH:35][CH3:34])=[O:24])[C:19]([F:20])([F:21])[F:22])=[O:16])[CH2:11][CH2:10]2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 6329MethylamineHCID 71656887HCID 71656887, compound

Product 1

HCID 71656889HCID 71656889, compoundYield 73.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of 1,1,1-trifluoro-3-methoxy-3-oxopropan-2-yl 4-(bis(4-chlorophenyl)methyl)piperazine-1-carboxylate (6h) (41 mg, 0.081 mmol) in THF (2 mL) was added methyl amine (0.81 mL, 0.81 mmol, 1.0M in THF). After stirring the reaction mixture for 24 h at room temperature, the reaction was quenched by the addition of aqueous 1N HCl (5 mL) and extracted with dichloromethane (3×, 25 mL). The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by SiO2 preparative TLC (50% EtOAc/hexanes) to give the title compound as a colorless oil (30 mg, 73%): 1H NMR 600 MHz (CDCl3) δ 7.31 (d, J=8.50 Hz, 4H), 7.27 (d, J=8.52 Hz, 4H), 6.05 (bs, 1H), 5.48 (q, J=7.10 Hz, 1H), 4.24 (s, 1H), 3.66-3.51 (m, 3H), 3.46 (dd, J=4.67, 15.51 Hz, 1H), 2.89 (d, J=4.90 Hz, 3H), 2.45 (d, J=8.91 Hz, 2H), 2.34 (t, J=16.23 Hz, 2H); HRMS m/z calc'd for [M+H]+ C22H22Cl2F3N3O3: 504.1063. found 504.1065.

Workup

  1. customthe reaction was quenched by the addition of aqueous 1N HCl (5 mL)
  2. extractionextracted with dichloromethane (3×, 25 mL)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product was purified by SiO2 preparative TLC (50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-9d0096dd086e4784b31f4212e5e451c7
Source dataset
uspto-grants-2015_09
Patent number
US09133148B2

Reaction notes

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