Sodium Carbonate → N-{4-[2-(4-fluorophenyl)-7-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl]pyridin-2-yl}propanamide

HRID 570136Notes

Reaction equation

HRID 570136 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17](B3OC(C)(C)C(C)(C)O3)=[C:11]3[O:12][CH2:13][CH2:14][CH:15]([CH3:16])[N:10]3[N:9]=2)=[CH:4][CH:3]=1.Br[C:28]1[CH:33]=[CH:32][N:31]=[C:30]([NH:34][C:35](=[O:38])[CH2:36][CH3:37])[CH:29]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.[Cl-].[Cl-].[Pd+2]>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:17]([C:28]3[CH:33]=[CH:32][N:31]=[C:30]([NH:34][C:35](=[O:38])[CH2:36][CH3:37])[CH:29]=3)=[C:11]3[O:12][CH2:13][CH2:14][CH:15]([CH3:16])[N:10]3[N:9]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 67073822N-(4-bromopyridin-2-yl)propanamideHCID 89488317HCID 89488317, compound

Product 1

HCID 89488349N-{4-[2-(4-fluorophenyl)-7-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl]pyridin-2-yl}propanamideYield 23.5%

Reagents, catalysts & solvents 2

HCID 11556747Bis(tricyclohexylphosphine)palladium(II) DichlorideCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

150 mg of 2-(4-fluorophenyl)-7-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine (0.419 mmol, 1.1 eq.) and 87 mg of N-(4-bromopyridin-2-yl)propanamide (0.381 mmol, 1 eq.) are dissolved in 1.5 ml of 1,4-dioxane. To this solution are added 22 mg of bis(tricyclohexylphosphine)-palladium(II)dichloride (0.03 mmol, 0.08 eq) and a aqueous solution of Na2CO3 (5 eq, 0.952 ml). The reaction mixture is flushed for 5 mins with argon and then sealed. Next the mixture is heated for 15 mins at 120° C. in the microwave (CEM Explorer). After cooling, the reaction mixture is diluted with EtOAc and washed with water. The combined organic phase are dried over Na2SO4 and concentrated in vacuo. The crude product is purified by silica gel chromatography (eluent cyclohexane/ethyl acetate). 34 mg (21%) of N-{4-[2-(4-fluorophenyl)-7-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl]pyridin-2-yl}propanamide are obtained.

Workup

  1. customThe reaction mixture is flushed for 5 mins with argon
  2. customsealed
  3. temperatureAfter cooling
  4. additionthe reaction mixture is diluted with EtOAc
  5. washwashed with water
  6. dry with materialThe combined organic phase are dried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe crude product is purified by silica gel chromatography (eluent cyclohexane/ethyl acetate)

Sources & evidence

ORD record
ord-fb6540000e2b499aa0536deabc6de2b9
Source dataset
uspto-grants-2015_05
Patent number
US09023844B2

Reaction notes

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