3-Chloro-2,5-diethylpyrazine → (1R,2S)-1-[(3,6-diethylpyrazin-2-yl)amino]-2,3-dihydro-1H-inden-2-ol

HRID 1824020Notes

Reaction equation

HRID 1824020 reaction equation
Cl[C:2]1[C:3]([CH2:10][CH3:11])=[N:4][CH:5]=[C:6]([CH2:8][CH3:9])[N:7]=1.[CH2:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C@@H:14]([NH2:21])[C@H:13]1[OH:22].CC(C)([O-])C.[Na+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C>[CH2:10]([C:3]1[C:2]([NH:21][C@@H:14]2[C:15]3[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH2:12][C@@H:13]2[OH:22])=[N:7][C:6]([CH2:8][CH3:9])=[CH:5][N:4]=1)[CH3:11]

Participants

7

Reactant 3

HCID 2373953-Chloro-2,5-diethylpyrazineHCID 2725045(1R,2S)-(+)-cis-1-Amino-2-indanolHCID 23676156Sodium t-butoxide

Product 1

HCID 58583341(1R,2S)-1-[(3,6-diethylpyrazin-2-yl)amino]-2,3-dihydro-1H-inden-2-olYield 65%

Reagents, catalysts & solvents 3

HCID 27342152-(Di-tert-butylphosphino)biphenylCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 3-chloro-2,5-diethylpyrazine (171 mg, 1.0 mmol), (1R,2S)-(+)-cis-1-amino-2-indanol (298 mg, 2.0 mmol), tris(dibenzylideneacetone)dipalladium (0) (28 mg, 0.03 mmol), and 2-(di-tertbutylphosphino)biphenyl (18 mg, 0.06 mmol) in toluene (2.0 mL) was purged with nitrogen and treated with sodium tertbutoxide (135 mg, 1.4 mmol). The resulting brown suspension was heated to 100° C. for 2 hours. At this time, the reaction was quenched with a saturated water solution of NaHCO3 and extracted twice with ethyl acetate (20 mL). The combined organics were washed with brine (15 mL), dried over MgSO4, filtered, and concentrated to give a black solid. This material was purified by biotage MPLC (40 g column, 25% ethyl acetate/heptane) to afford 184 mg (65%) of the title compound as a light purple solid. IR (diffuse reflectance) 3435, 3241, 2962, 2935, 2912, 2873, 1581, 1547, 1500, 1453, 1184, 1163, 1047, 744, 733 cm−1; OAMS supporting ions at: ESI+ 384.0; MS (CI) m/z 284 (MH+);

Workup

  1. customAt this time, the reaction was quenched with a saturated water solution of NaHCO3
  2. extractionextracted twice with ethyl acetate (20 mL)
  3. washThe combined organics were washed with brine (15 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a black solid
  8. customThis material was purified by biotage MPLC (40 g column, 25% ethyl acetate/heptane)

Sources & evidence

ORD record
ord-284d0f04d46a45518c1b401b39effe33
Source dataset
uspto-grants-2006_05
Patent number
US07041672B2

Reaction notes

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