Triethylamine → (3S,8S)-8-{(S)-2-[4-(2,3-Dimethyl-pyridin-4-yl)-phenyl]-1-methoxycarbonyl-ethyl-carbamoyl}-3-(3-hydroxy-phenyl)-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7-carboxylic acid tert-butyl ester

HRID 391827노트

반응식

HRID 391827 반응식
[C:1]([O:5][C:6]([N:8]1[C@H:17]([C:18](=[O:40])[NH:19][C@H:20]([C:36]([O:38][CH3:39])=[O:37])[CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]3[CH:33]=[CH:32][N:31]=[C:30]([CH3:34])[C:29]=3[CH3:35])=[CH:24][CH:23]=2)[CH2:16][C:15]2[CH:14]=[C:13]3[O:41][CH2:42][C@H:43]([C:45]4[CH:50]=[CH:49][CH:48]=[C:47]([O:51]CC5C=CC(Cl)=C(Cl)C=5)[CH:46]=4)[O:44][C:12]3=[CH:11][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C>CCOC(C)=O.CO.[Pd]>[C:1]([O:5][C:6]([N:8]1[C@H:17]([C:18](=[O:40])[NH:19][C@H:20]([C:36]([O:38][CH3:39])=[O:37])[CH2:21][C:22]2[CH:23]=[CH:24][C:25]([C:28]3[CH:33]=[CH:32][N:31]=[C:30]([CH3:34])[C:29]=3[CH3:35])=[CH:26][CH:27]=2)[CH2:16][C:15]2[CH:14]=[C:13]3[O:41][CH2:42][C@H:43]([C:45]4[CH:50]=[CH:49][CH:48]=[C:47]([OH:51])[CH:46]=4)[O:44][C:12]3=[CH:11][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

참가 물질

5

반응물 2

HCID 8471TriethylamineHCID 58327255(3S,8S)-3-[3-(3,4-Dichloro-benzyloxy)-phenyl]-8-{(S)-2-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-1-methoxycarbonyl-ethylcarbamoyl}-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7-carboxylic acid tert-butyl ester

생성물 1

HCID 58327272(3S,8S)-8-{(S)-2-[4-(2,3-Dimethyl-pyridin-4-yl)-phenyl]-1-methoxycarbonyl-ethyl-carbamoyl}-3-(3-hydroxy-phenyl)-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7-carboxylic acid tert-butyl ester수율 88.5%

시약·촉매·용매 2

HCID 23938Palladium촉매HCID 21584119Ethylacetate methanol용매

실험 절차

(3S,8S)-3-[3-(3,4-Dichloro-benzyloxy)-phenyl]-8-{(S)-2-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-1-methoxycarbonyl-ethylcarbamoyl}-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7-carboxylic acid tert-butyl ester (250 mg) was dissolved in 6 mL of EtOAc:MeOH (1:5) and Pd—C (30 mg, 10% by wt.) was added and stirred under a hydrogen atmosphere (balloon) for 4 hours. Triethylamine (0.3 mL) was added to the reaction mixture and stirred for 5 minutes. The catalyst was filtered and washed with MeOH. The filtrate was evaporated, and the residue was taken up in EtOAc (10 mL) and washed with water and brine, and then dried (Na2SO4), filtered, and evaporated to get (3S,8S)-8-{(S)-2-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-1-methoxycarbonyl-ethylcarbamoyl}-3-(3-hydroxy-phenyl)-2,3,8,9-tetrahydro-6H-[1,4]dioxino-[2,3-g]isoquinoline-7-carboxylic acid tert-butyl ester (180 mg). LCMS (m/z): 695.

후처리

  1. stirringstirred for 5 minutes
  2. filtrationThe catalyst was filtered
  3. washwashed with MeOH
  4. customThe filtrate was evaporated
  5. washwashed with water and brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated

출처 및 근거

ORD 기록
ord-73dc48ffa5ca4e09b7f56e0a44a64c63
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08383644B2

반응 노트

불러오는 중…