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 391827ノート

反応式

HRID 391827 の反応式
[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]

参加物

5

反応物 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

生成物 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 ester収率 88.5%

試薬・触媒・溶媒 2

HCID 23938Palladium触媒HCID 21584119Ethylacetate methanol溶媒

実験手順

(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.

後処理

  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

出典と根拠

ORDレコード
ord-73dc48ffa5ca4e09b7f56e0a44a64c63
出典データセット
uspto-grants-2013_02
特許番号
US08383644B2

反応ノート

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