HCID 90110263, compound → HCID 90113009, compound

HRID 1508899Notes

Reaction equation

HRID 1508899 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]([C:21]([CH3:27])([CH3:26])[C:22](OC)=[O:23])=[CH:17][CH:16]=3)[CH:11]=[C:10]([CH2:28][CH3:29])[N:9]=2)[CH:5]=[CH:6][CH:7]=1>C1COCC1>[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]([C:21]([CH3:26])([CH3:27])[CH2:22][OH:23])=[CH:19][CH:20]=3)[CH:11]=[C:10]([CH2:28][CH3:29])[N:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

3

Reactant 1

HCID 90110263HCID 90110263, compound

Product 1

HCID 90113009HCID 90113009, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
55 °C

Procedure

A 25-mL round bottom flask was charged with methyl 2-(4-((2-(3-chlorophenyl)-6-ethylpyrimidin-4-yl)methyl)phenyl)-2-methylpropanoate (0.259 g, 0.57 mmol) and THF (6 mL) at rt. Borane-dimethylsulfide complex (0.158 mL, 1.67 mmol) was added and the resulting solution was stirred at 55° C. for 2.5 h. LCMS analysis indicated only partial reduction. Borane-dimethylsulfide complex (0.100 mL, 1.05 mmol) was added and the resulting solution was stirred at 55° C. for a further 19 h until the starting material was consumed (monitored by LCMS analysis). The reaction was quenched with methanol then treated with 2N aqueous HCl (0.1 mL) and concentrated under reduced pressure. The residue was diluted with methanol and then concentrated under reduced pressure. The residue absorbed onto silica (2 g) then purified by column chromatography on silica using hexanes/ethyl acetate (10:0 to 0:10) as the eluent to afford the title compound (0.078 g, 36%) as a colorless oil. MW=380.91. 1H NMR (DMSO-d6, 500 MHz) δ 8.38-8.34 (m, 2H), 7.61-7.54 (m, 2H), 7.33-7.26 (m, 5H), 4.60 (t, J=5.5 Hz, 1H), 4.07 (s, 2H), 3.38 (d, J=5.5 Hz, 2H), 2.78 (q, J=7.5 Hz, 2H), 1.27 (t, J=7.5 Hz, 3H), 1.18 (s, 6H); APCI MS m/z 381 [M+H]+.

Workup

  1. additionBorane-dimethylsulfide complex (0.158 mL, 1.67 mmol) was added
  2. additionBorane-dimethylsulfide complex (0.100 mL, 1.05 mmol) was added
  3. stirringthe resulting solution was stirred at 55° C. for a further 19 h until the starting material
  4. customwas consumed (monitored by LCMS analysis)
  5. customThe reaction was quenched with methanol
  6. additionthen treated with 2N aqueous HCl (0.1 mL)
  7. concentrationconcentrated under reduced pressure
  8. additionThe residue was diluted with methanol
  9. concentrationconcentrated under reduced pressure
  10. customThe residue absorbed onto silica (2 g)
  11. customthen purified by column chromatography on silica

Sources & evidence

ORD record
ord-a9d1de074b7d48e48ec2758a2056f3f6
Source dataset
uspto-grants-2015_12
Patent number
US09221843B2

Reaction notes

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