Diisopropylethylamine → HCID 178480516、化合物

HRID 572877

反応式

HRID 572877 の反応式
Br[C:2]1[CH:3]=[C:4]([CH:8]([O:19][CH:20]2[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]2)[C:9]2[NH:13][C:12]3[CH:14]=[CH:15][C:16]([F:18])=[CH:17][C:11]=3[N:10]=2)[CH:5]=[CH:6][CH:7]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[C:69]([O:73][C:74](=[O:79])[NH:75][CH2:76][CH2:77][SH:78])([CH3:72])([CH3:71])[CH3:70].C(N(C(C)C)CC)(C)C>C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.[Pd].O1CCOCC1>[C:69]([O:73][C:74](=[O:79])[NH:75][CH2:76][CH2:77][S:78][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH:8]([C:9]2[NH:13][C:12]3[CH:14]=[CH:15][C:16]([F:18])=[CH:17][C:11]=3[N:10]=2)[O:19][CH:20]2[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]2)[CH:3]=1)([CH3:72])([CH3:70])[CH3:71]

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 3017761N-(tert-butoxycarbonyl)-2-aminoethanethiolHCID 178480509HCID 178480509、化合物

生成物 1

HCID 178480516HCID 178480516、化合物

試薬・触媒・溶媒 2

HCID 1542701,5-Diphenylpenta-1,4-dien-3-one;palladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
120 °C

実験手順

A screw-capped tube is charged with 2-[(3-bromophenyl)(1-methylpiperidin-4-yloxy)methyl]-5-fluoro-1H-benzimidazole (example 437D, 418 mg), palladium bis(dibenzylideneacetone) (30 mg), Xantphos (30 mg), (2-mercaptoethyl)carbamic acid tert-butyl ester (1 equivalent), diisopropylethylamine (180 μL) and 1,4-dioxane (6 mL). The tube is evacuated, filled with argon and sealed. After stirring at 120° C. overnight, the mixture is diluted with ethyl acetate and water and the aqueous phase is extracted with ethyl acetate. The pooled organic extracts are dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by chromatography (gradient dichloromethane/methanol from 98/2 to 95/5) to afford (2-{3-[(5-fluoro-1H-benzimidazol-2-yl)(1-methylpiperidin-4-yloxy)methyl]phenylsulfanyl}ethyl)carbamic acid tert-butyl ester. 1H NMR: 11.07 (sl, 1H), 7.69-7.59 (m, 1H), 7.39-7.36 (m, 1H), 7.30-7.15 (m, 2H), 7.04-6.91 (m, 2H), 5.83 (s, 1H), 5.30 (sl, 1H), 4.20 (s, 2H), 3.65-3.40 (m, 3H), 3.30-3.05 (m, 2H), 2.80-2.65 (m, 2H), 2.27 (s, 3H), 2.25-1.75 (m, 6H), 1.55 (s, 9H).

後処理

  1. customThe tube is evacuated
  2. additionfilled with argon
  3. customsealed
  4. additionthe mixture is diluted with ethyl acetate and water
  5. extractionthe aqueous phase is extracted with ethyl acetate
  6. dry with materialThe pooled organic extracts are dried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue is purified by chromatography (gradient dichloromethane/methanol from 98/2 to 95/5)

出典と根拠

ORDレコード
ord-545b275686da4b0985ff43a240fda21a
出典データセット
uspto-grants-2015_05
特許番号
US09029357B2

関連ノート

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