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Sodium Carbonate → N2-(2-chloro-5-((S)-2-hydroxypropylcarbamoyl)phenyl)-N2-methyl-N8-(2-(methylsulfonyl)ethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide

HRID 1849357
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인쇄 미리보기

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HRID 1849357 반응식
Br[C:2]1[CH:3]=[CH:4][C:5]2[C:11]3[S:12][C:13]([C:15]([N:17]([C:19]4[CH:24]=[C:23]([C:25](=[O:31])[NH:26][CH2:27][C@@H:28]([OH:30])[CH3:29])[CH:22]=[CH:21][C:20]=4[Cl:32])[CH3:18])=[O:16])=[CH:14][C:10]=3[CH2:9][CH2:8][O:7][C:6]=2[CH:33]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)[O:55][C:37]2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[CH3:76][S:77]([CH2:80][CH2:81][NH2:82])(=[O:79])=[O:78].Cl.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:32][C:20]1[CH:21]=[CH:22][C:23]([C:25](=[O:31])[NH:26][CH2:27][C@@H:28]([OH:30])[CH3:29])=[CH:24][C:19]=1[N:17]([CH3:18])[C:15]([C:13]1[S:12][C:11]2[C:5]3[CH:4]=[CH:3][C:2]([C:37]([NH:82][CH2:81][CH2:80][S:77]([CH3:76])(=[O:79])=[O:78])=[O:55])=[CH:33][C:6]=3[O:7][CH2:8][CH2:9][C:10]=2[CH:14]=1)=[O:16]
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참가 물질

8

반응물 4

HCID 10340Sodium CarbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 17749886Ethanamine, 2-(methylsulfonyl)-, hydrochloride (1:1)HCID 67050579HCID 67050579, 화합물

생성물 1

HCID 58204176N2-(2-chloro-5-((S)-2-hydroxypropylcarbamoyl)phenyl)-N2-methyl-N8-(2-(methylsulfonyl)ethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide
수율 423.9%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 1140Toluene용매HCID 6228Dimethylformamide용매

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온도
80 °C

실험 절차

A suspension of 8-bromo-N-(2-chloro-5-((S)-2-hydroxypropylcarbamoyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide (400 mg, 0.73 mmol), Pd(OAc)2 (8 mg, 0.037 mmol), Xantphos (42 mg, 0.073 mmol), MeSO2(CH2)2NH2.HCl (175 mg, 1.095 mmol) and Na2CO3 (232 mg, 2.19 mmol) in toluene (5 mL) and DMF (5 mL) was heated at 80° C. under atmosphere of CO from balloon overnight. Then it was filtrated and concentrated, the crude product was purified by pre-TLC (eluted by DCM: MeOH=10:1) to give 438 (191.9 mg, yield 42%). 1H NMR (DMSO-d6, 400 MHz): δ8.74 (t, J=5.2 Hz, 1H, NH), 8.62 (t, J=5.2 Hz, 1H, NH), 8.12-7.44 (m, 6H, ArH), 6.61 (s, 1H, ═CH), 4.77 (d, J=4.8 Hz, 1H, OH), 4.20 (br s, 2H, CH2), 3.80-3.75 (m, 1H, CH), 3.67-2.98 (m, 14H, CH3, CH2), 1.05 (t, J=6.0 Hz, 3H, CH3). LC-MS: (ESI, m/z)=620 [M+H]+

후처리

  1. filtrationThen it was filtrated
  2. concentrationconcentrated
  3. customthe crude product was purified by pre-TLC (eluted by DCM: MeOH=10:1)

출처 및 근거

ORD 기록
ord-102bd6d175a44d46816946320f2b25e4
출처 데이터셋
uspto-grants-2015_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08952043B2

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