Diisopropylethylamine → HCID 69217391, Verbindung

HRID 2251083Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2251083
[CH2:1]([O:3][C:4](=[O:35])[CH:5]=[C:6]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[Cl:34])[C:7]1[N:19]([C:20]2[C:25]([F:26])=[CH:24][CH:23]=[CH:22][C:21]=2[F:27])[C:10]2[N:11]=[C:12](S(C)(=O)=O)[N:13]=[CH:14][C:9]=2[CH:8]=1)[CH3:2].C(N(C(C)C)CC)(C)C.Cl.[NH2:46][CH:47]([CH3:52])[C:48]([CH3:51])([OH:50])[CH3:49]>CN1CCCC1=O.[NH4+].[Cl-]>[CH2:1]([O:3][C:4](=[O:35])[CH:5]=[C:6]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[Cl:34])[C:7]1[N:19]([C:20]2[C:25]([F:26])=[CH:24][CH:23]=[CH:22][C:21]=2[F:27])[C:10]2[N:11]=[C:12]([NH:46][CH:47]([CH3:52])[C:48]([OH:50])([CH3:51])[CH3:49])[N:13]=[CH:14][C:9]=2[CH:8]=1)[CH3:2]

Komponenten

6

Edukt 3

HCID 81531DiisopropylethylamineHCID 23434633HCID 23434633, Verbindung2×HCID 69218334HCID 69218334, Verbindung

Produkt 1

HCID 69217391HCID 69217391, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 13387N-methyl-2-pyrrolidoneLösungsmittelHCID 25517Ammonium ChlorideLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

To a solution of 3-(2-chloro-phenyl)-3-[7-(2,6-difluoro-phenyl)-2-methanesulfonyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-acrylic acid ethyl ester, 14, (0.30 g, 0.59 mmol)) in N-methylpyrrolidinone (4 mL) is added diisopropylethylamine (0.41 mL, 2.36 mmol) and 3-amino-2-methyl-butan-2-ol hydrochloride salt (0.10 g, 0.71 mmol). After heating the reaction at 90° C. for 21 hours, an additional equivalent of 3-amino-2-methyl-butan-2-ol hydrochloride salt (0.08 g, 0.59 mmol) is added and the mixture heated at 120° C. for 4 hours. The reaction is cooled to room temp and then diluted with aqueous saturated NH4Cl solution. The aqueous phase is twice extracted with CHCl3 and the organic phase is then washed with aqueous saturated NaHCO3 solution. The organic phase is dried (MgSO4), filtered, concentrated in vacuo and the resulting residue is purified by preparative HPLC to afford the desired product as a yellowish solid: 1H NMR (300 MHz, d3-DMSO) δ 8.64 (s, 1H), 7.64-7.52 (m, 1H), 7.38-7.24 (m, 5H), 7.14-7.08 (m, 1H), 6.57 (s, 1H), 5.95 (s, 1H), 4.31 (bd s, NH), 3.85 (q, J=7.2 Hz, 2H), 3.34 (m, 1H), 1.04 (s, 9H), 0.93 (t, J=7.2 Hz); ESI+ MS: m/z (rel intensity) 541.0 (100, M++H).

Aufarbeitung

  1. temperatureAfter heating
  2. customthe reaction at 90° C. for 21 hours
  3. temperatureThe reaction is cooled to room temp
  4. extractionThe aqueous phase is twice extracted with CHCl3
  5. washthe organic phase is then washed with aqueous saturated NaHCO3 solution
  6. dry with materialThe organic phase is dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customthe resulting residue is purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-09116be980114e7e8d4ef8556c39e9ce
Quelldatensatz
uspto-grants-2008_01
Patentnummer
US07319102B1

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