2-Bromopyrimidine → N-[(3R,4S)-4-ethoxy-1-pyrimidin-2-ylpyrrolidin-3-yl]-3,6-diethyl-5-(6-methoxy-2-methylpyridin-3-yl)pyrazin-2-amine

HRID 1297302Notes

Reaction equation

HRID 1297302 reaction equation
[CH2:1]([O:3][C@H:4]1[CH2:8][NH:7][CH2:6][C@H:5]1[NH:9][C:10]1[C:15]([CH2:16][CH3:17])=[N:14][C:13]([C:18]2[C:19]([CH3:26])=[N:20][C:21]([O:24][CH3:25])=[CH:22][CH:23]=2)=[C:12]([CH2:27][CH3:28])[N:11]=1)[CH3:2].Br[C:30]1[N:35]=[CH:34][CH:33]=[CH:32][N:31]=1.[Cl-].C(C1C=CC=C(C(C)C)C=1[N+]1C=CN(C2C(C(C)C)=CC=CC=2C(C)C)C=1)(C)C.CC(C)([O-])C.[K+].C(=O)(O)[O-].[Na+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:1]([O:3][C@H:4]1[CH2:8][N:7]([C:30]2[N:35]=[CH:34][CH:33]=[CH:32][N:31]=2)[CH2:6][C@H:5]1[NH:9][C:10]1[C:15]([CH2:16][CH3:17])=[N:14][C:13]([C:18]2[C:19]([CH3:26])=[N:20][C:21]([O:24][CH3:25])=[CH:22][CH:23]=2)=[C:12]([CH2:27][CH3:28])[N:11]=1)[CH3:2]

Participants

8

Reactant 5

HCID 783452-BromopyrimidineHCID 516892Sodium BicarbonateHCID 27349131,3-Bis(2,6-diisopropylphenyl)imidazolium chlorideHCID 23665647Potassium tert-butoxideHCID 58914560N-[(3R,4S)-4-ethoxypyrrolidin-3-yl]-3,6-diethyl-5-(6-methoxy-2-methylpyridin-3-yl)pyrazin-2-amine

Product 1

HCID 11374683N-[(3R,4S)-4-ethoxy-1-pyrimidin-2-ylpyrrolidin-3-yl]-3,6-diethyl-5-(6-methoxy-2-methylpyridin-3-yl)pyrazin-2-amineYield 52%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of N-[(3R,4S)-4-ethoxypyrrolidin-3-yl]-3,6-diethyl-5-(6-methoxy-2-methylpyridin-3-yl)pyrazin-2-amine (112 mg) in dioxane (1.45 ml) was added 2-bromo-pyrimidine (69 mg, 1.5 eq.), 1,3 Bis(2,6-di-i-propylphenyl)imidazolium chloride (20 mg, 0.16 eq.), Tris(dibenzylideneacetone)dipalladium (21 mg, 0.8 eq.) and potassium t-butoxide (49 mg, 1.5 eq.). The reaction mixture was heated at 100° C. for 16 h, poured into saturated sodium bicarbonate (50 ml), extracted 2×50 ml of CH2Cl2, dried MgSO4, filtered and concentrated. Purification via MPLC chromatography eluting with 20–50% ethyl acetate/heptane provided the title compound as an amorphous solid (70 mg, 52%):

Workup

  1. extractionextracted 2×50 ml of CH2Cl2, dried MgSO4
  2. filtrationfiltered
  3. concentrationconcentrated
  4. customPurification via MPLC chromatography
  5. washeluting with 20–50% ethyl acetate/heptane

Sources & evidence

ORD record
ord-67f612899e1f4471860e91812f3c2c50
Source dataset
uspto-grants-2007_07
Patent number
US07250418B2

Reaction notes

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