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Diisopropylethylamine → tert-Butyl [4-({[4-((3R,4R,5S)-3-[(tert-butoxycarbonyl)amino]-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methylpiperidin-1-yl)-2,3-dihydrofuro[2,3-b]pyridin-5-yl]amino}carbonyl)-2-(2,6-difluorophenyl)-1,3-thiazol-5-yl]carbamate

HRID 1499502
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HRID 1499502 반응식
[NH2:1][C:2]1[C:3]([N:11]2[CH2:16][C@H:15]([CH3:17])[C@@H:14]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])[C@H:13]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:12]2)=[C:4]2[CH2:10][CH2:9][O:8][C:5]2=[N:6][CH:7]=1.[C:34]([O:38][C:39]([NH:41][C:42]1[S:46][C:45]([C:47]2[C:52]([F:53])=[CH:51][CH:50]=[CH:49][C:48]=2[F:54])=[N:44][C:43]=1[C:55](O)=[O:56])=[O:40])([CH3:37])([CH3:36])[CH3:35].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[C:29]([O:28][C:27]([NH:26][C@H:13]1[C@H:14]([O:18][Si:19]([C:22]([CH3:23])([CH3:25])[CH3:24])([CH3:20])[CH3:21])[C@@H:15]([CH3:17])[CH2:16][N:11]([C:3]2[C:2]([NH:1][C:55]([C:43]3[N:44]=[C:45]([C:47]4[C:48]([F:54])=[CH:49][CH:50]=[CH:51][C:52]=4[F:53])[S:46][C:42]=3[NH:41][C:39](=[O:40])[O:38][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:56])=[CH:7][N:6]=[C:5]3[O:8][CH2:9][CH2:10][C:4]=23)[CH2:12]1)=[O:33])([CH3:32])([CH3:31])[CH3:30]
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참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 674381985-((Tert-butoxycarbonyl)amino)-2-(2,6-difluorophenyl)thiazole-4-carboxylic acidHCID 86726732tert-Butyl ((3R,4R,5S)-1-(5-amino-2,3-dihydrofuro[2,3-b]pyridin-4-yl)-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methylpiperidin-3-yl)carbamate

생성물 1

HCID 86726733
tert-Butyl [4-({[4-((3R,4R,5S)-3-[(tert-butoxycarbonyl)amino]-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methylpiperidin-1-yl)-2,3-dihydrofuro[2,3-b]pyridin-5-yl]amino}carbonyl)-2-(2,6-difluorophenyl)-1,3-thiazol-5-yl]carbamate
수율 25.2%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a mixture of tert-butyl ((3R,4R,5S)-1-(5-amino-2,3-dihydrofuro[2,3-b]pyridin-4-yl)-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methylpiperidin-3-yl)carbamate (67.8 mg, 0.142 mmol), 5-[(tert-butoxycarbonyl)amino]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxylic acid (65.4 mg, 0.184 mmol) and HATU (168.1 mg, 0.4421 mmol) was added DMF (2.0 mL) followed by DIPEA (144.5 mg, 1.118 mmol). The reaction mixture was stirred at room temperature for 3 h, and then concentrated under reduced pressure. The residue was purified by chromatography on silica gel (0-50% EtOAc in hexanes) to afford the sub-title compound as a brown solid (29.2 mg, 25%). LCMS calc. for C39H55F2N6O7SSi (M+H)+: m/z=817.4. found 817.3.

후처리

  1. concentrationconcentrated under reduced pressure
  2. customThe residue was purified by chromatography on silica gel (0-50% EtOAc in hexanes)

출처 및 근거

ORD 기록
ord-8d5d3dcecc6c4b008555cf787ea0218b
출처 데이터셋
uspto-grants-2015_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09200004B2

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