(2,4-Dichlorophenyl)boronic acid → methyl 3-(2,4-dichlorophenyl)-6-{[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}pyrazine-2-carboxylate

HRID 1824278Notes

Reaction equation

HRID 1824278 reaction equation
Br[C:2]1[C:3]([C:19]([O:21][CH3:22])=[O:20])=[N:4][C:5]([NH:8][C@@H:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH2:11][C@@H:10]2[OH:18])=[CH:6][N:7]=1.[Cl:23][C:24]1[CH:29]=[C:28]([Cl:30])[CH:27]=[CH:26][C:25]=1B(O)O>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>[Cl:23][C:24]1[CH:29]=[C:28]([Cl:30])[CH:27]=[CH:26][C:25]=1[C:2]1[C:3]([C:19]([O:21][CH3:22])=[O:20])=[N:4][C:5]([NH:8][C@@H:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH2:11][C@@H:10]2[OH:18])=[CH:6][N:7]=1

Participants

4

Reactant 2

HCID 2734659(2,4-Dichlorophenyl)boronic acidHCID 58583440methyl 3-bromo-6-{[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}pyrazine-2-carboxylate

Product 1

HCID 58583461methyl 3-(2,4-dichlorophenyl)-6-{[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}pyrazine-2-carboxylateYield 59.1%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
85 °C

Procedure

Charge a Kimble vial with methyl 3-bromo-6-{[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}pyrazine-2-carboxylate (0.45 g, 1.14 mmol), Pd(PPh3)4 (198 mg, 0.17 mmol), and 2,4-dichlorophenylboronic acid (325 mg, 1.71 mmol). Flush with N2 and add DMF (4 mL) and 2 M Na2CO3 (1.1 mL). The resulting mixture was heated at 85° C. overnight. The mixture was diluted with sat. aq. NaHCO3. Extract with Et2O. The organic extract was dried over MgSO4, filtered and concentrated. Purify by biotage MPLC (90 g column, 30% ethyl acetate/hexanes) to afford 290 mg (59%) of methyl 3-(2,4-dichlorophenyl)-6-{[(1R,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}pyrazine-2-carboxylate as a solid: 1H NMR (CDCl3) δ 3.06–3.09, 3.27–3.32, 3.80, 4.09–4.15, 4.84, 5.58, 7.28–7.49, 8.25; MS (ESI+) for C21H17Cl2N3O3 m/z 430 (M+H)+.

Workup

  1. customFlush with N2
  2. additionadd DMF (4 mL) and 2 M Na2CO3 (1.1 mL)
  3. additionThe mixture was diluted with sat. aq. NaHCO3
  4. extractionExtract with Et2O
  5. extractionThe organic extract
  6. dry with materialwas dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurify by biotage MPLC (90 g column, 30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-e1f1ebcd06d240828668d920f0cb9187
Source dataset
uspto-grants-2006_05
Patent number
US07041672B2

Reaction notes

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