2-(2-Hydroxyethyl)pyridine → tert-Butyl (3-{cyclopropyl[3-(3-methoxypropyl)-5-(2-pyridin-2-ylethoxy)benzyl]amino}-2-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]benzyl}-3-oxopropyl)carbamate

HRID 561877ノート

反応式

HRID 561877 の反応式
C1([C:4]2([N:7]([CH2:40][C:41]3[CH:46]=[C:45]([CH2:47][CH2:48][CH2:49][O:50][CH3:51])[CH:44]=[C:43]([OH:52])[CH:42]=3)[C:8](=[O:39])[CH:9]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][O:29][C:30]4[C:35]([Cl:36])=[CH:34][C:33]([CH3:37])=[CH:32][C:31]=4[Cl:38])=[CH:22][CH:21]=3)[CH2:10][NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH2:6][CH2:5]2)CC1.[N:53]1[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=1[CH2:59][CH2:60]O.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C(P(CCCC)CCCC)CCC>C1(C)C=CC=CC=1.CCOCC>[CH:4]1([N:7]([CH2:40][C:41]2[CH:42]=[C:43]([O:52][CH2:60][CH2:59][C:54]3[CH:55]=[CH:56][CH:57]=[CH:58][N:53]=3)[CH:44]=[C:45]([CH2:47][CH2:48][CH2:49][O:50][CH3:51])[CH:46]=2)[C:8](=[O:39])[CH:9]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][O:29][C:30]3[C:35]([Cl:36])=[CH:34][C:33]([CH3:37])=[CH:32][C:31]=3[Cl:38])=[CH:22][CH:21]=2)[CH2:10][NH:11][C:12](=[O:18])[O:13][C:14]([CH3:16])([CH3:17])[CH3:15])[CH2:5][CH2:6]1

参加物

7

反応物 4

HCID 76752-(2-Hydroxyethyl)pyridineHCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 86635933tert-Butyl (3-{cyclopropyl[3-hydroxy-5-(3-methoxypropyl)benzyl](cyclopropyl)amino}-2-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]benzyl}-3-oxopropyl)carbamate

生成物 1

HCID 86635939tert-Butyl (3-{cyclopropyl[3-(3-methoxypropyl)-5-(2-pyridin-2-ylethoxy)benzyl]amino}-2-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]benzyl}-3-oxopropyl)carbamate

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 3283Diethyl Ether溶媒

反応条件

温度
100 °C

実験手順

To a solution of tert-butyl (3-{cyclopropyl[3-hydroxy-5-(3-methoxypropyl)benzyl] (cyclopropyl)amino}-2-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]benzyl}-3-oxopropyl)carbamate from Example 70, Step 2 (1 eq.) in toluene (0.1 M) was added 2-pyridin-2-ylethanol (1.2 eq.) and 1,1′-(azodicarbonyl)-dipiperidine (1.2 eq.). The resulting orange solution was deoxygenated before tributylphosphine (1.2 eq.) was added. The now yellow-orange solution was heated at 100° C. for 14 h. The reaction mixture was cooled to RT, diluted with ether, and washed with 1 N aq. NaOH. The aqueous wash was back extracted with ether and the combined organic extracts were dried over MgSO4. Filtration and concentration of the filtrate in vacuo afforded a red oil. Purification of the crude product thus obtained by way of flash chromatography (SiO2, 4:1 (v/v) Hex:EtOAc→EtOAc) afforded the title compound as a pale yellow oil.

後処理

  1. additionwas added
  2. temperatureThe reaction mixture was cooled to RT
  3. washwashed with 1 N aq. NaOH
  4. washThe aqueous wash
  5. extractionwas back extracted with ether
  6. dry with materialthe combined organic extracts were dried over MgSO4
  7. filtrationFiltration and concentration of the filtrate in vacuo
  8. customafforded a red oil
  9. customPurification of the crude product
  10. customthus obtained by way of flash chromatography (SiO2, 4:1 (v/v) Hex:EtOAc→EtOAc)

出典と根拠

ORDレコード
ord-7ed98a70343f42148656a22fe93acaa6
出典データセット
uspto-grants-2011_11
特許番号
US08063105B2

反応ノート

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