Dichloromethane → HCID 58577919, compound

HRID 473961Notes

Reaction equation

HRID 473961 reaction equation
ClCCl.C(=O)([O-])[O-].[K+].[K+].[CH2:10]([CH:12]1[O:17][C:16]2[CH:18]=[C:19](B3OC(C)(C)C(C)(C)O3)[CH:20]=[CH:21][C:15]=2[NH:14][CH2:13]1)[CH3:11].Br[C:32]1[CH:33]=[N:34][C:35]([N:38]2[CH2:42][CH2:41][CH:40]([CH2:43][C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:39]2)=[N:36][CH:37]=1>O.O1CCOCC1>[CH2:10]([CH:12]1[O:17][C:16]2[CH:18]=[C:19]([C:32]3[CH:33]=[N:34][C:35]([N:38]4[CH2:42][CH2:41][CH:40]([CH2:43][C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:39]4)=[N:36][CH:37]=3)[CH:20]=[CH:21][C:15]=2[NH:14][CH2:13]1)[CH3:11]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 58577838HCID 58577838, compoundHCID 67995631HCID 67995631, compound

Product 1

HCID 58577919HCID 58577919, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

[1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (20.4 mg, 0.025 mmol), potassium carbonate (174.7 mg, 1.258 mmol), 2-ethyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine (prepared according to the procedure indicated in Scheme A1, 160.0 mg, 0.553 mmol) and tert-butyl 2-(1-(5-bromopyrimidin-2-yl)pyrrolidin-3-yl)acetate B-6 (172.1 mg, 0.503 mmol) were mixed in a 4:1 dioxane:water mixture (5.55 mL) at room temperature. The reaction mixture was degassed several times under reduced pressure and stirred for 12 h under an atmosphere of argon. The mixture was then filtered through a celite pad, washed with ethyl acetate (30 mL) and concentrated to dryness under reduced pressure. The residue was adsorbed on silica (1.0 g) and purified by flash column chromatography on silica gel (hexanes to ethyl acetate gradient) to give tert-butyl 2-(1-(5-(2-ethyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)pyrimidin-2-yl)pyrrolidin-3-yl)acetate B-7 as a light yellow oil (140.0 mg; Yield=60%). MS (ESI) [M+1]+ 425.

Workup

  1. customat room temperature
  2. customThe reaction mixture was degassed several times under reduced pressure
  3. filtrationThe mixture was then filtered through a celite pad
  4. washwashed with ethyl acetate (30 mL)
  5. concentrationconcentrated to dryness under reduced pressure
  6. custompurified by flash column chromatography on silica gel (hexanes to ethyl acetate gradient)

Sources & evidence

ORD record
ord-f69d7fa188cd4ff8910934e5bd44be29
Source dataset
uspto-grants-2014_01
Patent number
US08637507B2

Reaction notes

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