Sodium Carbonate → methyl (3R,4S)-3-{[3,6-diethyl-5-(6-methoxy-2,3-dihydro-1H-inden-5-yl)pyrazin-2-yl]amino}-4-ethoxypyrrolidine-1-carboxylate

HRID 1063273Notes

Reaction equation

HRID 1063273 reaction equation
[CH2:1]([C:3]1[C:4]([NH:12][C@H:13]2[C@@H:17]([O:18][CH2:19][CH3:20])[CH2:16][N:15]([C:21]([O:23][CH3:24])=[O:22])[CH2:14]2)=[N:5][C:6]([CH2:10][CH3:11])=[C:7](I)[N:8]=1)[CH3:2].[CH3:25][O:26][C:27]1[CH:35]=[C:34]2[C:30]([CH2:31][CH2:32][CH2:33]2)=[CH:29][C:28]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+].C([O-])(O)=O.[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>[CH2:1]([C:3]1[C:4]([NH:12][C@H:13]2[C@@H:17]([O:18][CH2:19][CH3:20])[CH2:16][N:15]([C:21]([O:23][CH3:24])=[O:22])[CH2:14]2)=[N:5][C:6]([CH2:10][CH3:11])=[C:7]([C:28]2[CH:29]=[C:30]3[C:34](=[CH:35][C:27]=2[O:26][CH3:25])[CH2:33][CH2:32][CH2:31]3)[N:8]=1)[CH3:2]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 516892Sodium BicarbonateHCID 22278823(6-methoxy-2,3-dihydro-1H-inden-5-yl)boronic acidHCID 86591415methyl (3R,4S)-3-[(3,6-diethyl-5-iodopyrazin-2-yl)amino]-4-ethoxypyrrolidine-1-carboxylate

Product 1

HCID 24887777methyl (3R,4S)-3-{[3,6-diethyl-5-(6-methoxy-2,3-dihydro-1H-inden-5-yl)pyrazin-2-yl]amino}-4-ethoxypyrrolidine-1-carboxylateYield 95%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A 7 ml vial was charged with methyl (3R,4S)-3-[(3,6-diethyl-5-iodopyrazin-2-yl)amino]-4-ethoxypyrrolidine-1-carboxylate (100 mg), 6-methoxy-2,3-dihydro-1H-inden-5-ylboronic acid (82 mg) (Preparation 2), tetrakis(triphenylphosphine)palladium (20 mg), 2 M Na2CO3 (0.4 mL), and ethylene glycol dimethyl ether (1.6 mL). The reaction was stirred for 18 hours at 80° C. The reaction was poured into sat. aq. NaHCO3 and extracted with ethyl ether. The organic phases were combined, dried with MgSO4, filtered, and concentrated. The crude was purified with flash column chromatography (silica, a gradient of 10-25% EtOAc in heptane) to give 97 mg, 95% of methyl (3R,4S)-3-{[3,6-diethyl-5-(6-methoxy-2,3-dihydro-1H-inden-5-yl)pyrazin-2-yl]amino}-4-ethoxypyrrolidine-1-carboxylate. IR (diffuse reflectance) 2967, 2934, 2876, 2350, 2335, 2224, 2063, 1940, 1710, 1568, 1482, 1466, 1451, 1392, 1348 cm−1 HRMS (ESI) calcd for C26H36N4O4+H1 469.2815. found 469.2805. Anal. Calcd for C26H36N4O4: C, 66.64; H, 7.74; N, 11.96. Found: C, 66.27; H, 7.61; N, 11.75.

Workup

  1. extractionextracted with ethyl ether
  2. dry with materialdried with MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude was purified with flash column chromatography (silica

Sources & evidence

ORD record
ord-5e1612bd5e924a3ab4c5a0db44f991aa
Source dataset
uspto-grants-2005_11
Patent number
US06964965B2

Reaction notes

Loading…