Potassium Carbonate → 2-[3-(hydroxymethyl)-4-[7-[[5-[4-(oxetan-3-yl)piperazin-1-yl]-2-pyridyl]amino]-3H-benzimidazol-5-yl]-2-pyridyl]-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1-one

HRID 1024084노트

반응식

HRID 1024084 반응식
Cl[C:2]1[CH:3]=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][N:21]([CH:24]4[CH2:27][O:26][CH2:25]4)[CH2:20][CH2:19]3)=[CH:14][N:13]=2)[C:5]2[N:9]=[CH:8][NH:7][C:6]=2[CH:10]=1.C([O:31][CH2:32][C:33]1[C:34]([N:48]2[CH2:60][CH2:59][N:51]3[C:52]4[CH2:53][CH2:54][CH2:55][CH2:56][C:57]=4[CH:58]=[C:50]3[C:49]2=[O:61])=[N:35][CH:36]=[CH:37][C:38]=1B1OC(C)(C)C(C)(C)O1)(=O)C.C(=O)([O-])[O-].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.O1CCOCC1.O>[OH:31][CH2:32][C:33]1[C:34]([N:48]2[CH2:60][CH2:59][N:51]3[C:52]4[CH2:53][CH2:54][CH2:55][CH2:56][C:57]=4[CH:58]=[C:50]3[C:49]2=[O:61])=[N:35][CH:36]=[CH:37][C:38]=1[C:2]1[CH:3]=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][N:21]([CH:24]4[CH2:25][O:26][CH2:27]4)[CH2:20][CH2:19]3)=[CH:14][N:13]=2)[C:5]2[N:9]=[CH:8][NH:7][C:6]=2[CH:10]=1

참가 물질

8

반응물 4

HCID 11430Potassium CarbonateHCID 75806TricyclohexylphosphineHCID 86684143(2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methyl acetateHCID 866841506-Chloro-N-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)-1H-benzo[d]imidazol-4-amine

생성물 1

HCID 715573052-[3-(hydroxymethyl)-4-[7-[[5-[4-(oxetan-3-yl)piperazin-1-yl]-2-pyridyl]amino]-3H-benzimidazol-5-yl]-2-pyridyl]-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1-one수율 15%

시약·촉매·용매 3

HCID 9832798Tris(dibenzylideneacetone) dipalladium촉매HCID 962Water용매HCID 312751,4-Dioxane용매

실험 절차

A microwave vial equipped with a magnetic stirrer was charged with 118b (200 mg, 0.52 mmol), 3-(acetoxymethyl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-4-ylboronic acid 114e (545 mg, 0.78 mmol), potassium carbonate (216 mg, 1.56 mmol), tris(dibenzylideneacetone) dipalladium(0) (48 mg, 0.052 mmol), tricyclohexylphosphine (146 mg, 0.52 mmol), water (0.2 mL), and dioxane (10 mL). After bubbling nitrogen through the suspension for 10 minutes, the sealed vial was irradiated under microwave at 110° C. for 1 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by reverse-phase prep-HPLC to afford 118 as a white solid (50 mg, 15%). MS-ESI: [M+H]+ 646.3. 1H NMR (500 MHz, DMSO) δ 8.69 (d, J=2.0 Hz, 1H), 8.49 (d, J=5.0 Hz, 1H), 8.32-8.28 (m, 2H), 8.13 (s, 1H), 7.85-7.83 (m, 1H), 7.39-7.33 (m, 2H), 7.36 (s, 1H), 7.29 (s, 1H), 6.59 (s, 1H), 5.89 (s, 1H), 4.56 (t, J=6.5 Hz, 2H), 4.46 (t, J=6.5 Hz, 2H), 4.23-4.16 (m, 2H), 4.15-4.12 (m, 4H), 3.89-3.53 (m, 1H), 3.13-3.07 (m, 5H), 2.64-2.54 (m, 2H), 2.51-2.43 (m, 5H), 1.79-1.70 (m, 4H)

후처리

  1. customA microwave vial equipped with a magnetic stirrer
  2. customAfter bubbling nitrogen through the suspension for 10 minutes
  3. customthe sealed vial was irradiated under microwave at 110° C. for 1 h
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by reverse-phase prep-HPLC

출처 및 근거

ORD 기록
ord-7e98e48907ea4b999f58b695c120e79c
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08722676B2

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