1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 86691760, Verbindung

HRID 1426988

Reaktionsgleichung

Reaktionsgleichung von HRID 1426988
[F:1][C:2]1([F:27])[CH2:6][N:5]([C:7]2[CH:12]=[CH:11][N:10]3[N:13]=[CH:14][C:15]([C:16](O)=[O:17])=[C:9]3[N:8]=2)[CH:4]([C:19]2[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:20]=2[OH:26])[CH2:3]1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[NH2:50][CH2:51][C@H:52]([OH:55])[CH2:53][Cl:54].CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[Cl:54][CH2:53][C@@H:52]([OH:55])[CH2:51][NH:50][C:16]([C:15]1[CH:14]=[N:13][N:10]2[CH:11]=[CH:12][C:7]([N:5]3[CH2:6][C:2]([F:1])([F:27])[CH2:3][CH:4]3[C:19]3[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:20]=3[OH:26])=[N:8][C:9]=12)=[O:17]

Komponenten

8

Edukt 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 1350101-Amino-3-chloro-2-propanol hydrochloride, (S)-HCID 67470704HCID 67470704, Verbindung

Produkt 1

HCID 86691760HCID 86691760, VerbindungAusbeute 105 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a mixture of 5-(4,4-difluoro-2-(5-fluoro-2-hydroxyphenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (0.047 g, 0.124 mmol) and HOBT (0.0252 g, 0.186 mmol) in DMF (1 mL) at ambient temperature was added EDCI (0.0357 g, 0.186 mmol). The resulting mixture was stirred for 1 hour. To this mixture was added (S)-1-amino-3-chloropropan-2-ol hydrochloride (Example 19, Step A; 0.0218 g, 0.149 mmol) followed by DIEA (0.0656 mL, 0.373 mmol) at ambient temperature. The resulting mixture was stirred for 48 hours. The reaction mixture was diluted with EtOAc (10 mL), and the organic layer was washed with a 1:1 mixture of brine and water. The aqueous layer was separated and extracted with EtOAc (2×10 mL). The combined organic layers were washed with a 1:1 mixture of brine and water (15 mL) and combined with the organic layer obtained previously. The organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure to afford N-((S)-3-chloro-2-hydroxypropyl)-5-(4,4-difluoro-2-(5-fluoro-2-hydroxyphenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (0.061 g, 105% yield). LC/MS (ES+APCI) m/z=468.1 (M−H).

Aufarbeitung

  1. stirringThe resulting mixture was stirred for 48 hours
  2. washthe organic layer was washed with a 1:1 mixture of brine and water
  3. customThe aqueous layer was separated
  4. extractionextracted with EtOAc (2×10 mL)
  5. washThe combined organic layers were washed with a 1:1 mixture of brine and water (15 mL)
  6. customobtained previously
  7. dry with materialThe organic layer was dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-b7f18fc37b744e648aff6357e3443e98
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08933084B2

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