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

HRID 1499426Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1499426
[C:1]([O:5][C:6]([NH:8][C:9]1[S:13][C:12]([C:14]2[C:19]([F:20])=[CH:18][CH:17]=[CH:16][C:15]=2[F:21])=[N:11][C:10]=1[C:22]([OH:24])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:25][C:26]1[C:27]([N:35]2[CH2:40][CH2:39][CH2:38][C@H:37]([NH:41][C:42](=[O:48])[O:43][C:44]([CH3:47])([CH3:46])[CH3:45])[CH2:36]2)=[C:28]2[CH2:34][CH2:33][O:32][C:29]2=[N:30][CH:31]=1.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>CCOC(C)=O.CN(C=O)C>[C:1]([O:5][C:6]([NH:8][C:9]1[S:13][C:12]([C:14]2[C:15]([F:21])=[CH:16][CH:17]=[CH:18][C:19]=2[F:20])=[N:11][C:10]=1[C:22]([NH:25][C:26]1[C:27]([N:35]2[CH2:40][CH2:39][CH2:38][C@H:37]([NH:41][C:42](=[O:48])[O:43][C:44]([CH3:46])([CH3:45])[CH3:47])[CH2:36]2)=[C:28]2[CH2:34][CH2:33][O:32][C:29]2=[N:30][CH:31]=1)=[O:24])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Komponenten

7

Edukt 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 86726677tert-Butyl [(3S)-1-(5-amino-2,3-dihydrofuro[2,3-b]pyridin-4-yl)piperidin-3-yl]carbamate

Produkt 1

HCID 86726678tert-Butyl {(3S)-1-[5-({[5-[(tert-butoxycarbonyl)amino]-2-(2,6-difluorophenyl)-1,3-thiazol-4-yl]carbonyl}amino)-2,3-dihydrofuro[2,3-b]pyridin-4-yl]piperidin-3-yl}carbamateAusbeute 95 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a mixture of 5-[(tert-butoxycarbonyl)amino]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxylic acid (Example 1, Step 6, 418.2 mg, 1.174 mmol), tert-butyl [(3S)-1-(5-amino-2,3-dihydrofuro[2,3-b]pyridin-4-yl)piperidin-3-yl]carbamate (377.4 mg, 1.128 mmol) and HATU (1308 mg, 3.440 mmol), DMF (15.0 mL) was added, followed by DIPEA (1.00 mL, 5.74 mmol). The mixture was stirred at room temperature for 2 h. The reaction mixture was then diluted with EtOAc (150 mL), washed with saturated aq. NaHCO3 (150 mL) and brine (2×75 mL), then dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (0-100% EtOAc in hexanes) to give the sub-title compound as a yellow solid (720.2 mg, 95%). LCMS calc. for C32H39F2N6O6S (M+H)+: m/z=673.3. found 673.2.

Aufarbeitung

  1. additionwas added
  2. washwashed with saturated aq. NaHCO3 (150 mL) and brine (2×75 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by chromatography on silica gel (0-100% EtOAc in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-c032acfdb2fc4b399cbc7cba587cadd9
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09200004B2

Notizen zur Reaktion

Wird geladen…