7-Chloro-2H,4H-1,3-benzodioxine-2,4-dione → N-[2-Benzyloxy-4-(4,6-bis-((3R,5S)-3,5-bis-(tert-Butoxycarbonylamino)-piperidin-1-yl)-[1,3,5]triazin-2-ylamino)-phenyl]-4-chloro-2-hydroxy-benzamide

HRID 1354823노트

반응식

HRID 1354823 반응식
[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([NH:15][C:16]2[N:21]=[C:20]([N:22]3[CH2:27][C@@H:26]([NH:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][C@@H:24]([NH:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:23]3)[N:19]=[C:18]([N:44]3[CH2:49][C@@H:48]([NH:50][C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:47][C@@H:46]([NH:58][C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])[CH2:45]3)[N:17]=2)[CH:12]=[CH:11][C:10]=1[NH2:66])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:67][C:68]1[CH:79]=[CH:78][C:71]2[C:72](=O)[O:73]C(=O)[O:75][C:70]=2[CH:69]=1>CN1C(=O)CCC1.CCOC(C)=O>[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([NH:15][C:16]2[N:21]=[C:20]([N:22]3[CH2:27][C@@H:26]([NH:28][C:29]([O:31][C:32]([CH3:33])([CH3:34])[CH3:35])=[O:30])[CH2:25][C@@H:24]([NH:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:23]3)[N:19]=[C:18]([N:44]3[CH2:45][C@@H:46]([NH:58][C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])[CH2:47][C@@H:48]([NH:50][C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:49]3)[N:17]=2)[CH:12]=[CH:11][C:10]=1[NH:66][C:72](=[O:73])[C:71]1[CH:78]=[CH:79][C:68]([Cl:67])=[CH:69][C:70]=1[OH:75])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

참가 물질

5

반응물 2

HCID 211038237-Chloro-2H,4H-1,3-benzodioxine-2,4-dioneHCID 588651042-Benzyloxy-N4-(4,6-bis-((3R,5S)-3,5-bis-(tert-butoxycarbonylamino)-piperidin-1-yl)-[1,3,5]triazin-2-yl)-benzene-1,4-diamine

생성물 1

HCID 58865029N-[2-Benzyloxy-4-(4,6-bis-((3R,5S)-3,5-bis-(tert-Butoxycarbonylamino)-piperidin-1-yl)-[1,3,5]triazin-2-ylamino)-phenyl]-4-chloro-2-hydroxy-benzamide수율 60%

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 13387N-methyl-2-pyrrolidone용매

반응 조건

온도
80 °C

실험 절차

2-Benzyloxy-N4-(4,6-bis-((3R,5S)-3,5-bis-(tert-butoxycarbonylamino)-piperidin-1-yl)-[1,3,5]triazin-2-yl)-benzene-1,4-diamine (83) (0.16 g, 0.174 mmol) and 7-chloro-benzo[1,3]dioxine-2,4-dione (91) (0.2 g, 1.0 mmol) were combined and dissolved in NMP (8 mL). The mixture was heated to 80° C. for 16 h. LC-MS indicated complete reaction at this point. The mixture was diluted with EtOAc (30 mL), washed with water (2×15 mL), saturated aqueous NaHCO3 (2×15 mL) and brine (2×15 mL) via extraction, dried over MgSO4 and concentrated to give a brown oil. Purification by flash chromatography on silica gel using a gradient of hexane and EtOAc (15–100% EtOAc in hexane) gave the desired product (92) as a yellow powder upon concentration (0.111 g, 0.103 mmol, 60% yield). LC-MS (ESI): (exact mass: 1073.51) m/e=1074.6 [M+1]+ (100%).

후처리

  1. customreaction at this point
  2. washwashed with water (2×15 mL), saturated aqueous NaHCO3 (2×15 mL) and brine (2×15 mL) via extraction
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customto give a brown oil
  6. customPurification by flash chromatography on silica gel using a gradient of hexane and EtOAc (15–100% EtOAc in hexane)

출처 및 근거

ORD 기록
ord-45ecdc8911d344b3990e06e7aeef65d8
출처 데이터셋
uspto-grants-2007_05
특허 번호
US07223759B2

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