Diisopropylethylamine → N-(2'-oxo-1',2',5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2-yl)-2-[2-oxo-3-(1,3-thiazol-2-yl)-2,3-dihydro-1H-benzimidazol-1-yl]acetamide

HRID 1921227노트

반응식

HRID 1921227 반응식
[O:1]=[C:2]1[N:6]([CH2:7][C:8]([OH:10])=O)[C:5]2[CH:11]=[CH:12][CH:13]=[CH:14][C:4]=2[N:3]1[C:15]1[S:16][CH:17]=[CH:18][N:19]=1.[NH2:20][C:21]1[N:26]=[C:25]2[CH2:27][C:28]3([CH2:38][C:24]2=[CH:23][CH:22]=1)[C:36]1[C:31](=[N:32][CH:33]=[CH:34][CH:35]=1)[NH:30][C:29]3=[O:37].C1CN(C(Cl)=[N+]2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>C1COCC1>[O:37]=[C:29]1[NH:30][C:31]2=[N:32][CH:33]=[CH:34][CH:35]=[C:36]2[C:28]21[CH2:27][C:25]1=[N:26][C:21]([NH:20][C:8](=[O:10])[CH2:7][N:6]3[C:5]4[CH:11]=[CH:12][CH:13]=[CH:14][C:4]=4[N:3]([C:15]4[S:16][CH:17]=[CH:18][N:19]=4)[C:2]3=[O:1])=[CH:22][CH:23]=[C:24]1[CH2:38]2

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 27366521-(Chloro-1-pyrrolidinylmethylene)pyrrolidinium HexafluorophosphateHCID 57974056(+/-)-2-Amino-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one2회HCID 67354298[2-oxo-3-(1,3-thiazol-2-yl)-2,3-dihydro-1H-benzimidazol-1-yl]acetic acid2회

생성물 1

HCID 25143871N-(2'-oxo-1',2',5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2-yl)-2-[2-oxo-3-(1,3-thiazol-2-yl)-2,3-dihydro-1H-benzimidazol-1-yl]acetamide

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

A mixture of [2-oxo-3-(1,3-thiazol-2-yl)-2,3-dihydro-1H-benzimidazol-1-yl]acetic acid (62 mg, 0.23 mmol, described in Intermediate 33), (±)-2-amino-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (71 mg, 0.28 mmol, described in Intermediate 5), N,N,N′,N′-bis(tetramethylene)chloroformamidinium hexafluorophosphate (153 mg, 0.46 mmol), and N,N-diisopropylethylamine (0.20 mL, 1.15 mmol) in THF (2 mL) is stirred at ambient temperature for 18 h. The reaction mixture is purified directly by HPLC using a reversed phase C18 column and eluting with a gradient of H2O:CH3CN:CF3CO2H—90:10:0.1 to 5:95:0.1. The pure, product-containing fractions are combined and made basic with saturated aqueous NaHCO3. The resulting mixture is extracted with EtOAc (3×20 mL), and the combined organic extracts are washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to provide the title compound.

후처리

  1. customThe reaction mixture is purified directly by HPLC
  2. washeluting with a gradient of H2O
  3. additionThe pure, product-containing fractions
  4. extractionThe resulting mixture is extracted with EtOAc (3×20 mL)
  5. washthe combined organic extracts are washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-c7a836d956f4418fa1f93fc04fa0ffbc
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08173655B2

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