Tetrahydrofuran → HCID 60026346, compound

HRID 400677Notes

Reaction equation

HRID 400677 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:11]([CH3:32])([CH3:31])[CH2:12][C:13]([OH:30])([C:26]([F:29])([F:28])[F:27])[CH2:14][C:15]2[NH:23][C:22]3[C:17](=[N:18][C:19]([C:24]#N)=[CH:20][CH:21]=3)[CH:16]=2)[C:5]2[O:9][CH2:8][CH2:7][C:6]=2[CH:10]=1.[CH:33]([Mg]Cl)([CH3:35])[CH3:34].C1C[O:41]CC1>>[Cl:1][C:2]1[CH:3]=[C:4]([C:11]([CH3:32])([CH3:31])[CH2:12][C:13]([OH:30])([C:26]([F:28])([F:29])[F:27])[CH2:14][C:15]2[NH:23][C:22]3[C:17](=[N:18][C:19]([C:24](=[O:41])[CH:33]([CH3:35])[CH3:34])=[CH:20][CH:21]=3)[CH:16]=2)[C:5]2[O:9][CH2:8][CH2:7][C:6]=2[CH:10]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 11712374HCID 11712374, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 60026346HCID 60026346, compoundYield 70%

Conditions

Temperature
75 °C

Procedure

2-[4-(5-Chloro-2,3-dihydrobenzofuran-7-yl)-2-hydroxy-4-methyl-2-trifluoromethylpentyl]-1H-pyrrolo[3,2-b]pyridine-5-carbonitrile (50 mg, 0.11 mmol) was dissolved in 3 mL of THF. Isopropyl magnesium chloride (2 M in THF, 0.15 mL, 0.3 mmol) was added, followed by CuBr (7 mg, 0.05 mmol). The reaction was stirred at reflux (75° C.) for 30 minutes. The mixture was cooled to room temperature. The reaction was quenched with 1 mL of water, followed by 3 drops of concentrated HCl. The mixture was stirred for 10 minutes, and neutralized with saturated sodium carbonate solution until the pH was 8. The reaction mixture was extracted with ethyl acetate and washed with brine. The solvent was removed in vacuo. The residue was purified by preparative HPLC (medium polar condition) to give the title compound (39 mg, 70% yield).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. customThe reaction was quenched with 1 mL of water
  3. stirringThe mixture was stirred for 10 minutes
  4. extractionThe reaction mixture was extracted with ethyl acetate
  5. washwashed with brine
  6. customThe solvent was removed in vacuo
  7. customThe residue was purified by preparative HPLC (medium polar condition)

Sources & evidence

ORD record
ord-75ad42abe77049c9912f44ca49797cdc
Source dataset
uspto-grants-2014_06
Patent number
US08741897B2

Reaction notes

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