Tributylvinyltin → (1R,2S)-1-{[5-(2,4-dichlorophenyl)-6-methoxy-3-vinylpyrazin-2-yl]amino}-2,3-dihydro-1H-inden-2-ol

HRID 1612372Notes

Reaction equation

HRID 1612372 reaction equation
Br[C:2]1[C:3]([NH:18][C@@H:19]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH2:21][C@@H:20]2[OH:28])=[N:4][C:5]([O:16][CH3:17])=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][C:9]=2[Cl:15])[N:7]=1.[CH2:29]([Sn](CCCC)(CCCC)C=C)[CH2:30]CC.[F-].[K+]>CN(C=O)C.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:15][C:9]1[CH:10]=[C:11]([Cl:14])[CH:12]=[CH:13][C:8]=1[C:6]1[N:7]=[C:2]([CH:29]=[CH2:30])[C:3]([NH:18][C@@H:19]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH2:21][C@@H:20]2[OH:28])=[N:4][C:5]=1[O:16][CH3:17]

Participants

6

Reactant 3

HCID 81998TributylvinyltinHCID 522689Potassium FluorideHCID 58631236(1R,2S)-1-{[3-bromo-5-(2,4-dichlorophenyl)-6-methoxypyrazin-2-yl]amino}-2,3-dihydro-1H-inden-2-ol

Product 1

HCID 58631243(1R,2S)-1-{[5-(2,4-dichlorophenyl)-6-methoxy-3-vinylpyrazin-2-yl]amino}-2,3-dihydro-1H-inden-2-olYield 99.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of (1R,2S)-1-{[3-bromo-5-(2,4-dichlorophenyl)-6-methoxypyrazin-2-yl]amino}-2,3-dihydro-1H-inden-2-ol (150 mg, 0.31 mmol) in DMF (1.6 mL) is added Pd(PPh3)4 (7 mg, 6 μmol), and tributyl vinyl tin (114 mg, 0.36 mmol). The reaction is heated at 120° C. overnight. Sat. aq. KF (15 mL) is added and the mixture is stirred at rt for 1 hr. Extract with CH2Cl2 (5×30 mL). The combined organic extracts were dried over MgSO4, filtered and concentrated. Purify by biotage MPLC (90 g column, 15% ethyl acetate/hexanes) to afford 132 mg (38%) of (1R,2S)-1-{[5-(2,4-dichlorophenyl)-6-methoxy-3-vinylpyrazin-2-yl]amino}-2,3-dihydro-1H-inden-2-ol as a solid: 1H NMR (CDCl3) δ 3.08-3.12, 3.28-3.34, 3.93, 4.82, 5.46-5.49, 5.54-5.67, 6.09-6.13, 6.77-6.84, 7.28-7.50; MS (ESI+) for C20H17Cl2N3O2 m/z 402 (M+H)+.

Workup

  1. extractionExtract with CH2Cl2 (5×30 mL)
  2. dry with materialThe combined organic extracts were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurify by biotage MPLC (90 g column, 15% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-2aad4df7f14e46f6b0c839f662622d02
Source dataset
uspto-grants-2006_01
Patent number
US06992087B2

Reaction notes

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