Tetrahydrofuran → HCID 86725394, compound

HRID 1503841Notes

Reaction equation

HRID 1503841 reaction equation
[C:1]([C:4]1[C:5]2[N:6]([CH:33]=[N:34][N:35]=2)[C:7](SC)=[N:8][C:9]=1[NH:10][C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]2)=[CH:13][C:12]=1[F:30])(=[O:3])[NH2:2].[Br-].[Cl:37][C:38]1[CH:45]=[CH:44][CH:43]=[C:42]([Cl:46])[C:39]=1[CH2:40][Zn+].O1CCCC1>ClCCl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([C:4]1[C:5]2[N:6]([CH:33]=[N:34][N:35]=2)[C:7]([CH2:40][C:39]2[C:38]([Cl:37])=[CH:45][CH:44]=[CH:43][C:42]=2[Cl:46])=[N:8][C:9]=1[NH:10][C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]2)=[CH:13][C:12]=1[F:30])(=[O:3])[NH2:2]

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 86725393HCID 86725393, compoundHCID 178478100HCID 178478100, compound

Product 1

HCID 86725394HCID 86725394, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
70 °C

Procedure

To a mixture of the product of Example 28E (200 mg, 0.4 mmol) and tetrakis(triphenylphosphine)palladium (50 mg, 0.04 mmol) was added 0.5M 2,6-dichlorobenzylzinc bromide in tetrahydrofuran (4 mL, 2 mmol) under nitrogen atmosphere and the mixture was heated at 70° C. for 16 hours. After cooling to ambient temperature, the mixture was diluted with dichloromethane (50 mL) and washed with saturated aqueous sodium bicarbonate. The organic phase was separated and the aqueous phase was extracted with dichloromethane (2×20 mL). The combined organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography on silica gel (200-300 mesh) eluting with 97/3 dichloromethane/methanol to give the title compound. MS: 615 (M+H+).

Workup

  1. temperatureAfter cooling to ambient temperature
  2. washwashed with saturated aqueous sodium bicarbonate
  3. customThe organic phase was separated
  4. extractionthe aqueous phase was extracted with dichloromethane (2×20 mL)
  5. washThe combined organic phase was washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash chromatography on silica gel (200-300 mesh)
  10. washeluting with 97/3 dichloromethane/methanol

Sources & evidence

ORD record
ord-b5ee66770a224d78a6d60e8339f890eb
Source dataset
uspto-grants-2015_12
Patent number
US09212192B2

Reaction notes

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