Triethylamine → tert-butyl 4-[3-((3R)-3-{[(1S)-1-(5-bromopyridin-3-yl)-3-tert-butoxy-3-oxopropyl]carbamoyl}piperidin-1-yl)-3-oxopropyl]piperidine-1-carboxylate

HRID 526380ノート

反応式

HRID 526380 の反応式
[NH2:1][C@H:2]([C:11]1[CH:12]=[N:13][CH:14]=[C:15]([Br:17])[CH:16]=1)[CH2:3][C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5].O=C1CCC(=O)N1[O:25][C:26]([C@@H:28]1[CH2:33][CH2:32][CH2:31][N:30]([C:34](=[O:50])[CH2:35][CH2:36][CH:37]2[CH2:42][CH2:41][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:39][CH2:38]2)[CH2:29]1)=O.C(N(CC)CC)C>CN(C=O)C.ClCCl>[Br:17][C:15]1[CH:16]=[C:11]([C@@H:2]([NH:1][C:26]([C@@H:28]2[CH2:33][CH2:32][CH2:31][N:30]([C:34](=[O:50])[CH2:35][CH2:36][CH:37]3[CH2:42][CH2:41][N:40]([C:43]([O:45][C:46]([CH3:48])([CH3:47])[CH3:49])=[O:44])[CH2:39][CH2:38]3)[CH2:29]2)=[O:25])[CH2:3][C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5])[CH:12]=[N:13][CH:14]=1

参加物

6

反応物 3

HCID 8471TriethylamineHCID 71259769tert-butyl (3S)-3-amino-3-(5-bromopyridin-3-yl)propanoateHCID 89407588tert-butyl 4-{3-[(3R)-3-{[(2,5-dioxopyrrolidin-1-yl)oxy]carbonyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate2 回

生成物 1

HCID 71259834tert-butyl 4-[3-((3R)-3-{[(1S)-1-(5-bromopyridin-3-yl)-3-tert-butoxy-3-oxopropyl]carbamoyl}piperidin-1-yl)-3-oxopropyl]piperidine-1-carboxylate収率 72.9%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

To tert-butyl (3S)-3-amino-3-(5-bromopyridin-3-yl)propanoate (1.33 g, 4.42 mmol) in DMF (17 mL) was added tert-butyl 4-{3-[(3R)-3-{[(2,5-dioxopyrrolidin-1-yl)oxy]carbonyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate (example 25c 2.54 g, 4.91 mmol) and triethylamine (1.85 mL, 13.2 mmol) in dichloromethane (17 mL) at 0° C. After 3 hours the mixture was quenched by addition of saturated aqueous ammonium chloride solution, phases were separated and the aqueous phase was extracted with diethyl ether. Combined organic extracts were dried over sodium sulphate, concentrated under reduced pressure and the residue was purified by chromatography on silica gel (ethyl acetate in hexane, 12 to 100% followed by methanol in ethyl acetate 0 to 15%) to yield 2.1 g of tert-butyl 4-[3-((3R)-3-{[(1S)-1-(5-bromopyridin-3-yl)-3-tert-butoxy-3-oxopropyl]carbamoyl}piperidin-1-yl)-3-oxopropyl]piperidine-1-carboxylate.

後処理

  1. customAfter 3 hours the mixture was quenched by addition of saturated aqueous ammonium chloride solution, phases
  2. customwere separated
  3. extractionthe aqueous phase was extracted with diethyl ether
  4. dry with materialCombined organic extracts were dried over sodium sulphate
  5. concentrationconcentrated under reduced pressure
  6. customthe residue was purified by chromatography on silica gel (ethyl acetate in hexane, 12 to 100% followed by methanol in ethyl acetate 0 to 15%)

出典と根拠

ORDレコード
ord-8748c418dff1486d8f123f608ec06e04
出典データセット
uspto-grants-2016_05
特許番号
US09345793B2

反応ノート

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