Sodium Carbonate → 3,6-diethyl-N-(1-ethylpropyl)-5-(6-methoxy-2,3-dihydro-1H-inden-5-yl)pyrazin-2-amine

HRID 1063257Notes

Reaction equation

HRID 1063257 reaction equation
Br[C:2]1[N:3]=[C:4]([CH2:16][CH3:17])[C:5]([NH:10][CH:11]([CH2:14][CH3:15])[CH2:12][CH3:13])=[N:6][C:7]=1[CH2:8][CH3:9].[CH3:18][O:19][C:20]1[CH:28]=[C:27]2[C:23]([CH2:24][CH2:25][CH2:26]2)=[CH:22][C:21]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+]>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.COCCOC>[CH2:16]([C:4]1[C:5]([NH:10][CH:11]([CH2:14][CH3:15])[CH2:12][CH3:13])=[N:6][C:7]([CH2:8][CH3:9])=[C:2]([C:21]2[CH:22]=[C:23]3[C:27](=[CH:28][C:20]=2[O:19][CH3:18])[CH2:26][CH2:25][CH2:24]3)[N:3]=1)[CH3:17]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 222488495-bromo-3,6-diethyl-N-(1-ethylpropyl)pyrazin-2-amineHCID 22278823(6-methoxy-2,3-dihydro-1H-inden-5-yl)boronic acid

Product 1

HCID 98421773,6-diethyl-N-(1-ethylpropyl)-5-(6-methoxy-2,3-dihydro-1H-inden-5-yl)pyrazin-2-amineYield 66.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A scintillation vial with a Teflon lined cap was charged with 5-bromo-3,6-diethyl-N-(1-ethylpropyl)pyrazin-2-amine (300.2 mg, 1 mmol), 6-methoxy-2,3-dihydro-1H-inden-5-ylboronic acid (211.2 mg, 1.1 mmol, Preparation 2), terakis(triphenylphosphine)palladium (0) (116 mg, 0.1 mmol), 2M Na2CO3 (1 mL, 2 mmol), and ethylene glycol dimethyl ether (6 mL). The reaction was heated on the orbital shaker to 80° C. for 30 hours. After cooling to ambient temperature, the reaction was partitioned between H2O and ethyl acetate. The aqueous layer was extracted one more time with ethyl acetate. The organics were combined, dried with Na2SO4, filtered and concentrated to 530 mg of a yellow crude oil. The crude was purified by Biotage MPLC (90 g column, 1.5% acetone in toluene) to give 243 mg (66%) of 3,6-diethyl-N-(1-ethylpropyl)-5-(6-methoxy-2,3-dihydro-1H-inden-5-yl)pyrazin-2-amine as a pale yellow oil. Rf 0.19 (10% ethyl acetate in heptane). IR (liq.) 2964, 2935, 2874, 1566, 1550, 1484, 1464, 1444, 1391, 1380, 1276, 1253, 1203, 1174, 1033 cm−1. OAMS supporting ions at: ESI+368.3. HRMS (ESI) calcd for C23H33N3O+H1 368.2702, found 368.2703. Anal. Calcd for C23H33N3O: C, 75.16; H, 9.05; N, 11.43. Found: C, 75.25; H, 9.15; N, 11.13.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. customthe reaction was partitioned between H2O and ethyl acetate
  3. extractionThe aqueous layer was extracted one more time with ethyl acetate
  4. dry with materialdried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated to 530 mg of a yellow crude oil
  7. customThe crude was purified by Biotage MPLC (90 g column, 1.5% acetone in toluene)

Sources & evidence

ORD record
ord-a00399578a28464f97f0ef3f93db0baa
Source dataset
uspto-grants-2005_11
Patent number
US06964965B2

Reaction notes

Loading…