Hydrochloric Acid → HCID 90338489, compound

HRID 1508893Notes

Reaction equation

HRID 1508893 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([CH2:21][C:22](Cl)=[O:23])=[CH:17][CH:16]=3)[CH:11]=[C:10]([CH2:25][CH3:26])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[CH3:27][NH:28][CH2:29][CH2:30][CH3:31].C(N(C(C)C)CC)(C)C.Cl>ClCCl.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([CH2:14][C:15]3[CH:16]=[CH:17][C:18]([CH2:21][C:22]([N:28]([CH3:27])[CH2:29][CH2:30][CH3:31])=[O:23])=[CH:19][CH:20]=3)[CH:11]=[C:10]([CH2:25][CH3:26])[N:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 12315N-MethylpropylamineHCID 81531DiisopropylethylamineHCID 90111445HCID 90111445, compound

Product 1

HCID 90338489HCID 90338489, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of crude 2-(4-((2-(3-chlorophenyl)-6-ethylpyrimidin-4-yl)methyl)phenyl)acetyl chloride (˜0.20 mmol) in dichloromethane (8 mL) at 0° C. was added N-methyl-n-propylamine (0.10 mL, 1.00 mmol) followed by diisopropylethylamine (0.17 mL, 1.00 mmol). After stirring for 3 h the reaction mixture was diluted with dichloromethane (50 mL) and water (5 mL). The mixture was acidified with 2N aqueous HCl until pH˜5. The organic layer was washed with saturated sodium chloride (5 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica using hexanes/ethyl acetate (10:0 to 1:1) as eluent followed by preparative HPLC (water/acetonitrile with 0.05% TFA) to afford the title compound (0.040 g, 48%) as a colorless oil. MW=421.96. 1H NMR (DMSO-d6, 500 MHz) δ 8.37-8.33 (m, 2H), 7.59 (dt, J=7.5, 2.0 Hz, 1H), 7.55 (t, J=7.5 Hz, 1H), 7.29 (d, J=8.0 Hz, 2H), 7.25 (d, J=5.5 Hz, 1H), 7.18 (t, J=8.0 Hz, 2H), 4.10 (s, 2H), 3.63 (d, J=4.0 Hz, 2H), 3.27-3.19 (m, 2H), 2.94 (s, 1.6H), 2.81-2.79 (m, 3.4H), 1.47-1.37 (m, 2H), 1.26 (t, J=7.5 Hz, 3H), 0.80-0.73 (m, 3H); APCI MS m/z 422 [M+H]+.

Workup

  1. washThe organic layer was washed with saturated sodium chloride (5 mL)
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by chromatography on silica

Sources & evidence

ORD record
ord-8740fe8af5a841579ed76f843cbff22c
Source dataset
uspto-grants-2015_12
Patent number
US09221843B2

Reaction notes

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