(S)-tert-butyl 4-(4-(5-bromopyrimidin-2-ylamino)phenethyl)-2,2-dimethyloxazolidine-3-carboxylate → (S)-tert-butyl 4-(4-(5-tert-butylpyrimidin-2-ylamino)phenethyl)-2,2-dimethyloxazolidine-3-carboxylate

HRID 1187774Notes

Reaction equation

HRID 1187774 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([NH:8][C:9]2[CH:30]=[CH:29][C:12]([CH2:13][CH2:14][C@H:15]3[CH2:19][O:18][C:17]([CH3:21])([CH3:20])[N:16]3[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[CH:11][CH:10]=2)=[N:6][CH:7]=1.[Br-].[C:32]([Zn+])([CH3:35])([CH3:34])[CH3:33]>C1COCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[C:32]([C:2]1[CH:3]=[N:4][C:5]([NH:8][C:9]2[CH:30]=[CH:29][C:12]([CH2:13][CH2:14][C@H:15]3[CH2:19][O:18][C:17]([CH3:21])([CH3:20])[N:16]3[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[CH:11][CH:10]=2)=[N:6][CH:7]=1)([CH3:35])([CH3:34])[CH3:33]

Participants

5

Reactant 2

HCID 67501307(S)-tert-butyl 4-(4-(5-bromopyrimidin-2-ylamino)phenethyl)-2,2-dimethyloxazolidine-3-carboxylateHCID 178455669HCID 178455669, compound

Product 1

HCID 67502410(S)-tert-butyl 4-(4-(5-tert-butylpyrimidin-2-ylamino)phenethyl)-2,2-dimethyloxazolidine-3-carboxylateYield 9%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
22 °C

Procedure

To (S)-tert-butyl 4-(4-(5-bromopyrimidin-2-ylamino)phenethyl)-2,2-dimethyloxazolidine-3-carboxylate (100 mg) and bis(tri-t-butylphosphine)palladium(0) (21.4 mg) in THF (10 ml) under argon was added tert-butylzinc(II) bromide (1.26 ml, 0.5 M solution in THF). The reaction mixture was stirred at 22° C. for 1 hour. The reaction was quenched by addition of EtOAc then washed sequentially with saturated aqueous ammonium chloride solution and 1 N aqueous sodium bicarbonate solution. The phases were separated and the organic phase was dried over MgSO4, filtered and then concentrated in vacuo. The crude material was purified by preparative HPLC (Column: Zorbax 5 micron C18 50×20, flow rate: 30 ml/min; eluant gradient: water (+0.1% formic acid)/acetonitrile (80%-20% to 5%-95%)) to afford (S)-tert-butyl 4-(4-(5-tert-butylpyrimidin-2-ylamino)phenethyl)-2,2-dimethyloxazolidine-3-carboxylate (8.4 mg, 9%) as a yellow oil. MS (ISP): 455.5 ([M+H]+).

Workup

  1. customThe reaction was quenched by addition of EtOAc
  2. washthen washed sequentially with saturated aqueous ammonium chloride solution and 1 N aqueous sodium bicarbonate solution
  3. customThe phases were separated
  4. dry with materialthe organic phase was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by preparative HPLC (Column: Zorbax 5 micron C18 50×20, flow rate: 30 ml/min; eluant gradient: water (+0.1% formic acid)/acetonitrile (80%-20% to 5%-95%))

Sources & evidence

ORD record
ord-b9072b6d50664f35983ddc40d4476079
Source dataset
uspto-grants-2014_03
Patent number
US08673950B2

Reaction notes

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