Triethylamine → methyl 4-(4-(5-amino-6-(1H-benzo[d]imidazol-2-yl)pyrazin-2-yl)-5,6-dihydropyridin-1(2H)-yl)-4-oxobutanoate

HRID 1959440노트

반응식

HRID 1959440 반응식
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[C:11]([NH2:22])=[N:12][CH:13]=[C:14]([C:16]2[CH2:17][CH2:18][NH:19][CH2:20][CH:21]=2)[N:15]=1.Cl[C:24](=[O:31])[CH2:25][CH2:26][C:27]([O:29][CH3:30])=[O:28].C(N(CC)CC)C>C(Cl)Cl>[NH2:22][C:11]1[N:12]=[CH:13][C:14]([C:16]2[CH2:17][CH2:18][N:19]([C:24](=[O:31])[CH2:25][CH2:26][C:27]([O:29][CH3:30])=[O:28])[CH2:20][CH:21]=2)=[N:15][C:10]=1[C:2]1[NH:3][C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[N:1]=1

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 73888Butanoic acid, 4-chloro-4-oxo-, methyl esterHCID 667451703-(1H-benzo[d]imidazol-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)pyrazin-2-amine

생성물 1

HCID 66745179methyl 4-(4-(5-amino-6-(1H-benzo[d]imidazol-2-yl)pyrazin-2-yl)-5,6-dihydropyridin-1(2H)-yl)-4-oxobutanoate

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of 3-(1H-benzimidazol-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)pyrazin-2-amine (50 mg, 0.12 mmol) in DCM (2 mL) at 0° C. was added methyl 4-chloro-4-oxo-butanoate (19 mg, 15 μL, 0.12 mmol) followed by the addition of triethylamine (50 mg, 69 μL, 0.5 mmol). The reaction mixture was stirred at room temperature for 2 h and then partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc, dried (MgSO4), filtered and concentrated. The crude material was dissolved in DMSO and purified by reverse phase HPLC using 1-99% MeOH in H2O to obtain methyl 4-(4-(5-amino-6-(1H-benzo[d]imidazol-2-yl)pyrazin-2-yl)-5,6-dihydropyridin-1(2H)-yl)-4-oxobutanoate, which was re-dissolved in THF (1.0 mL), treated with NaOH (996 μL of 2.5 M, 2.5 mmol) and stirred for 18 h at room temperature. The reaction mixture was then acidified with conc. HCl till pH7 and extracted with DCM. The organic layer was dried (MgSO4), filtered and concentrated. The crude material was purified via reverse phase HPLC using 1-99% MeOH in H2O (0.05% HCl modifier) to obtain 4-(4-(5-amino-6-(1H-benzo[d]imidazol-2-yl)pyrazin-2-yl)-5,6-dihydropyridin-1(2H)-yl)-4-oxobutanoic acid (5 mg, 11%). 1H NMR (400 MHz, MeOD) δ 8.24 (s, 1H), 7.66 (d, J=4.1 Hz, 2H), 7.27 (dd, J=6.0, 3.1 Hz, 2H), 6.68 (d, J=7.9 Hz, 1H), 4.34 (s, 1H), 4.27 (s, 1H), 3.84 (t, J=5.6 Hz, 2H), 2.85 (s, 1H), 2.80-2.65 (m, 3H), 2.56-2.47 (m, 2H). LC/MS m/z 393.0 [M+H]+.

후처리

  1. custompartitioned between EtOAc and water
  2. extractionThe aqueous layer was extracted with EtOAc
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe crude material was dissolved in DMSO
  7. custompurified by reverse phase

출처 및 근거

ORD 기록
ord-960c73c78fe445019bd041393f9fca2c
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08410112B2

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