Potassium Carbonate → (R)-methyl 1-isopropyl-2-(5-(methoxycarbonyl)-4-methylpyrimidin-2-yl)-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate

HRID 1521533Notes

Reaction equation

HRID 1521533 reaction equation
Cl[C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][N:5]=[C:4]([N:12]2[CH2:17][CH2:16][N:15]3[C:18]4[CH:24]=[C:23]([S:25]([CH3:28])(=[O:27])=[O:26])[C:22]([C:29]([O:31][CH3:32])=[O:30])=[CH:21][C:19]=4[N:20]=[C:14]3[C@H:13]2[CH:33]([CH3:35])[CH3:34])[N:3]=1.[CH3:36]B1OB(C)OB(C)O1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.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>[CH:33]([C@H:13]1[N:12]([C:4]2[N:3]=[C:2]([CH3:36])[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][N:5]=2)[CH2:17][CH2:16][N:15]2[C:18]3[CH:24]=[C:23]([S:25]([CH3:28])(=[O:27])=[O:26])[C:22]([C:29]([O:31][CH3:32])=[O:30])=[CH:21][C:19]=3[N:20]=[C:14]12)([CH3:35])[CH3:34]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 574072TrimethylboroxineHCID 117927157(R)-methyl 2-(4-chloro-5-(methoxycarbonyl)pyrimidin-2-yl)-1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate

Product 1

HCID 89815891(R)-methyl 1-isopropyl-2-(5-(methoxycarbonyl)-4-methylpyrimidin-2-yl)-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylateYield 75%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of (R)-methyl 2-(4-chloro-5-(methoxycarbonyl)pyrimidin-2-yl)-1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate (20 mg, 0.04 mmol) and 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane (50 mg, 0.4 mmol) in 5 mL of dioxane was added K2CO3 (54 mg, 0.4 mmol) followed by Pd(PPh3)4 (5 mg, 0.004 mmol) under N2 with stirring. The mixture was refluxed for 2 h until the material was disappeared. The reaction mixture was cooled to rt. The dioxane was removed under vacuum. Water (10 mL) was added and the mixture was extracted with EtOAc (10 mL×3). The organic layers were dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The residue was purified by preparative TLC to afford (R)-methyl 1-isopropyl-2-(5-(methoxycarbonyl)-4-methylpyrimidin-2-yl)-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate (15 mg, 75% yield) as a colorless oil. LC-MS MS (ESI) m/z 502.1 [M+H]+.

Workup

  1. temperatureThe mixture was refluxed for 2 h until the material
  2. customThe dioxane was removed under vacuum
  3. additionWater (10 mL) was added
  4. extractionthe mixture was extracted with EtOAc (10 mL×3)
  5. dry with materialThe organic layers were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified by preparative TLC

Sources & evidence

ORD record
ord-8712b741a265410880fb873a38c70676
Source dataset
uspto-grants-2015_07
Patent number
US09073931B2

Reaction notes

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