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1,4-Dioxane → Benzyl [2-[({4-[(3R,4S,5S)-3-[(tert-butoxycarbonyl)amino]-5-methyl-4-(1H-1,2,3-triazol-1-yl)piperidin-1-yl]pyridin-3-yl}amino)carbonyl]-7-(3,6-dihydro-2H-pyran-4-yl)quinolin-3-yl]carbamate

HRID 924509
ノート
印刷プレビュー

反応式

HRID 924509 の反応式
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:41][C:42](=[O:51])[O:43][CH2:44][C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)[C:8]([C:12]([NH:14][C:15]3[CH:16]=[N:17][CH:18]=[CH:19][C:20]=3[N:21]3[CH2:26][C@H:25]([CH3:27])[C@H:24]([N:28]4[CH:32]=[CH:31][N:30]=[N:29]4)[C@H:23]([NH:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:22]3)=[O:13])=[N:9]2)=[CH:4][CH:3]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1.CC1(C)C(C)(C)OB([C:74]2[CH2:75][CH2:76][O:77][CH2:78][CH:79]=2)O1>C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.NC1C=CC=CC=1C1C=CC=CC=1[Pd]Cl.O>[C:37]([O:36][C:34]([NH:33][C@H:23]1[C@@H:24]([N:28]2[CH:32]=[CH:31][N:30]=[N:29]2)[C@@H:25]([CH3:27])[CH2:26][N:21]([C:20]2[CH:19]=[CH:18][N:17]=[CH:16][C:15]=2[NH:14][C:12]([C:8]2[C:7]([NH:41][C:42](=[O:51])[O:43][CH2:44][C:45]3[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=3)=[CH:6][C:5]3[C:10](=[CH:11][C:2]([C:74]4[CH2:79][CH2:78][O:77][CH2:76][CH:75]=4)=[CH:3][CH:4]=3)[N:9]=2)=[O:13])[CH2:22]1)=[O:35])([CH3:39])([CH3:38])[CH3:40]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 86726948Benzyl {7-bromo-2-[({4-[(3R,4S,5S)-3-[(tert-butoxycarbonyl)amino]-5-methyl-4-(1H-1,2,3-triazol-1-yl)piperidin-1-yl]pyridin-3-yl}amino)carbonyl]quinolin-3-yl}carbamate

生成物 1

HCID 86726949
Benzyl [2-[({4-[(3R,4S,5S)-3-[(tert-butoxycarbonyl)amino]-5-methyl-4-(1H-1,2,3-triazol-1-yl)piperidin-1-yl]pyridin-3-yl}amino)carbonyl]-7-(3,6-dihydro-2H-pyran-4-yl)quinolin-3-yl]carbamate
収率 27%

試薬・触媒・溶媒 2

HCID 178439015HCID 178439015、化合物触媒HCID 962Water溶媒

反応条件

温度
90 °C

実験手順

A pressure tube was charged with benzyl {7-bromo-2-[({4-[(3R,4S,5S)-3-[(tert-butoxycarbonyl)amino]-5-methyl-4-(1H-1,2,3-triazol-1-yl)piperidin-1-yl]pyridin-3-yl}amino)carbonyl]quinolin-3-yl}carbamate (15 mg, 0.020 mmol), K3PO4 (8.4 mg, 0.04 mmol), 1,4-dioxane (0.3 mL), water (0.04 mL) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyran (6.3 mg, 0.03 mmol). The reaction mixture was purged with nitrogen for 10 min., then dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine-(2′-aminobiphenyl-2-yl)(chloro)palladium (1:1) (1.6 mg, 0.002 mmol) was added. The pressure tube was sealed and the reaction mixture was heated at 90° C. for 30 min then allowed to cool. The mixture was then filtered and purified by preparative LCMS (pH=10 method; XBridge™ preparative C18 5 μm OBD™ column, 30×10 mm, 60 mL/min., eluting with a gradient of MeCN and water with 0.1% NH4OH) to give the sub-title compound as a light yellow powder (4 mg, 27%). LCMS calc. for C41H46N9O6 (M+H)+: m/z=760.4. Found: 760.5.

後処理

  1. customThe reaction mixture was purged with nitrogen for 10 min.
  2. customThe pressure tube was sealed
  3. temperatureto cool
  4. filtrationThe mixture was then filtered
  5. custompurified by preparative LCMS (pH=10 method
  6. washXBridge™ preparative C18 5 μm OBD™ column, 30×10 mm, 60 mL/min., eluting with a gradient of MeCN and water with 0.1% NH4OH)

出典と根拠

ORDレコード
ord-029045f92b3e41dc85d1f8fd39e54f68
出典データセット
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09278950B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート