Water → HCID 69264825, compound

HRID 917611Notes

Reaction equation

HRID 917611 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:10]([NH:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([Cl:21])[CH:14]=2)=[N:9][C:8](Cl)=[CH:7][N:6]=1)=[O:4].[OH:23][CH2:24][CH:25]1[CH2:29][CH2:28][CH2:27][NH:26]1.C(N(CC)CC)C.O>O1CCCC1>[CH3:1][O:2][C:3]([C:5]1[C:10]([NH:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([Cl:21])[CH:14]=2)=[N:9][C:8]([N:26]2[CH2:27][CH2:28][CH2:29][C@H:25]2[CH2:24][OH:23])=[CH:7][N:6]=1)=[O:4]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 90908Prolinol2×HCID 22665590HCID 22665590, compound

Product 1

HCID 69264825HCID 69264825, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-methoxycarbonyl-3-(3-chloro-4-methoxybenzylamino)-5-chloropyrazine (prepared in 297-(3)) 150 mg, 2-hydroxymethylpyrrolidine 88.6 mg and triethylamine 0.12 ml in tetrahydrofuran 5 ml is stirred for 4 hours at room temperature and heated at 50° C. for 2 hours. Then 2-hydroxymethylpyrrolidine 44.3 mg is added thereto and the mixture is heated at 50° C. for 1 hour. After cooling, water is added thereto and the solution is extracted with ethyl acetate. The extract is washed with water and brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The resulting yellowish oil is purified with silica gel frash column chromatography (solvent; chloroform:hexane=1:1) to give (S)-2-methoxycarbonyl-3-(3-chloro-4-methoxybenzylamino)-5-(2-hydroxymethyl-1-pyrrolidinyl)pyrazine as a pale yellowish powder, 123 mg. MS(m/z): 407(M+H)+

Workup

  1. temperatureheated at 50° C. for 2 hours
  2. temperaturethe mixture is heated at 50° C. for 1 hour
  3. temperatureAfter cooling
  4. extractionthe solution is extracted with ethyl acetate
  5. washThe extract is washed with water and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe resulting yellowish oil is purified with silica gel frash column chromatography (solvent; chloroform:hexane=1:1)

Sources & evidence

ORD record
ord-2222928c89b34045a84c636ef6c5e7e5
Source dataset
uspto-grants-2007_09
Patent number
US07273868B2

Reaction notes

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