1-(5-(2-Fluorophenyl)pyrimidin-2-yl)-6-(morpholine-4-carbonyl)-1H-indole-3-carbaldehyde → (1-(5-(2-Fluorophenyl)pyrimidin-2-yl)-3-(1-hydroxyethyl)-1H-indol-6-yl)(morpholino)-methanone

HRID 630457Notes

Reaction equation

HRID 630457 reaction equation
[CH3:1][Mg]I.[F:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[CH:12]=[N:13][C:14]([N:17]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:26]([N:28]4[CH2:33][CH2:32][O:31][CH2:30][CH2:29]4)=[O:27])[CH:24]=3)[C:19]([CH:34]=[O:35])=[CH:18]2)=[N:15][CH:16]=1>C1COCC1>[F:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[CH:16]=[N:15][C:14]([N:17]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:26]([N:28]4[CH2:33][CH2:32][O:31][CH2:30][CH2:29]4)=[O:27])[CH:24]=3)[C:19]([CH:34]([OH:35])[CH3:1])=[CH:18]2)=[N:13][CH:12]=1

Participants

4

Reactant 2

HCID 1186660411-(5-(2-Fluorophenyl)pyrimidin-2-yl)-6-(morpholine-4-carbonyl)-1H-indole-3-carbaldehydeHCID 178418373HCID 178418373, compound

Product 1

HCID 118666316(1-(5-(2-Fluorophenyl)pyrimidin-2-yl)-3-(1-hydroxyethyl)-1H-indol-6-yl)(morpholino)-methanone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Methyl magnesium iodide (3M solution in diethyl ether, 0.17 mL, 0.522 mmol, 1.5 eq) was added at −70° C. to a stirred solution of 28a) (150 mg, 0.348 mmol, 1.0 eq) in dry THF (10 mL) and stirring was continued for 2 h at −50° C. The reaction mixture was quenched with ammonium chloride solution, diluted with water (20 mL), and extracted with ethyl acetate (2×20 mL). The organic layers were washed with brine, dried over sodium sulfate, and evaporated. The residue was purified by preparative TLC using 70% ethyl acetate in petrolether as eluent. White solid. Yield: 70 mg (45% of theory). Melting range: 209-213° C. HPLC (method 1): Rt=10.09 min. Mass spectroscopy: m/z: [M+H]+=447.0.

Workup

  1. customThe reaction mixture was quenched with ammonium chloride solution
  2. additiondiluted with water (20 mL)
  3. extractionextracted with ethyl acetate (2×20 mL)
  4. washThe organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. customThe residue was purified by preparative TLC

Sources & evidence

ORD record
ord-0a00544ccb4e405fac94f2b2f7ffc0a0
Source dataset
uspto-grants-2016_04
Patent number
US09315490B2

Reaction notes

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