Diisopropylethylamine → HCID 178480516, 화합물

HRID 572877

반응식

HRID 572877 반응식
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]

참가 물질

7

반응물 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, 화합물

생성물 1

HCID 178480516HCID 178480516, 화합물

시약·촉매·용매 2

HCID 1542701,5-Diphenylpenta-1,4-dien-3-one;palladium촉매HCID 312751,4-Dioxane용매

반응 조건

온도
120 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-545b275686da4b0985ff43a240fda21a
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09029357B2

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