Potassium Carbonate → HCID 89741701, compound

HRID 1526975Notes

Reaction equation

HRID 1526975 reaction equation
Br[C:2]1[C:3]([NH:9][C@@H:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH3:11])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[C:18]([O:23][CH3:24])(=[O:22])[C:19]#[C:20][CH3:21].[Cl-].[Li+].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:8][C:5]1[N:6]=[CH:7][C:2]2[C:19]([C:18]([O:23][CH3:24])=[O:22])=[C:20]([CH3:21])[N:9]([C@@H:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH3:11])[C:3]=2[N:4]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 141019Methyl but-2-ynoateHCID 433294Lithium ChlorideHCID 60124244HCID 60124244, compound

Product 1

HCID 89741701HCID 89741701, compoundYield 15.2%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A solution of (R)-5-bromo-2-chloro-N-(1-phenylethyl)pyrimidin-4-amine (5 g, 16 mmol), methyl but-2-ynoate (3.1 g, 32 mmol), lithium chloride (690 mg, 16 mmol), potassium carbonate (5.5 g, 40 mmol) and palladium acetate (360 mg, 1.6 mmol) in N,N-dimethylformamide (50 mL) was degassed and back-filled with nitrogen for three times, then heated at 120° C. for 4 hours. The reaction mixture was filtered and the filtrate was concentrated in vacuo, extracted with ethyl acetate (50 mL), washed with water (50 mL), dried over anhydrous magnesium sulfate and purified by column chromatography (silica gel, petroleum ether/ethyl acetate=5:1) to give (R)-methyl 2-chloro-6-methyl-7-(1-phenylethyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate as a yellow oil (800 mg, 15%). LRMS (M+H+) m/z: calcd 329.09. found 329. 1H NMR (300 MHz, CDCl3): δ 9.16 (s, 1H), 7.39-7.18 (m, 5H), 6.45-6.42 (m, 1H), 3.96 (s, 3H), 2.57 (s, 3H), 2.05 (d, J=7.2 Hz, 3H).

Workup

  1. additionback-filled with nitrogen for three times
  2. filtrationThe reaction mixture was filtered
  3. concentrationthe filtrate was concentrated in vacuo
  4. extractionextracted with ethyl acetate (50 mL)
  5. washwashed with water (50 mL)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. custompurified by column chromatography (silica gel, petroleum ether/ethyl acetate=5:1)

Sources & evidence

ORD record
ord-086f9135ff274cf385ca3d058e2e5b4e
Source dataset
uspto-grants-2015_07
Patent number
US09085583B2

Reaction notes

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