Diisopropylamine → HCID 67260932, Verbindung

HRID 410714

Reaktionsgleichung

Reaktionsgleichung von HRID 410714
C(NC(C)C)(C)C.[Li+].CCC[CH2-].OC1C(O)([C:21]2[S:22][C:23]([C:26]3[CH:31]=[C:30]([NH:32][C:33]4[N:38]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:36]=[CH:35][N:34]=4)[CH:29]=[C:28]([CH3:43])[CH:27]=3)=[CH:24][N:25]=2)CCNC(=O)C1.[O:46]1[C:50]2([CH2:55][CH2:54][C:53](=[N:56][S:57]([C:59]([CH3:62])([CH3:61])[CH3:60])=[O:58])[CH2:52][CH2:51]2)[O:49][CH2:48][CH2:47]1>O1CCCC1.ClCCl.CO>[CH3:60][C:59]([S:57]([NH:56][C:53]1([C:21]2[S:22][C:23]([C:26]3[CH:31]=[C:30]([NH:32][C:33]4[N:38]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:36]=[CH:35][N:34]=4)[CH:29]=[C:28]([CH3:43])[CH:27]=3)=[CH:24][N:25]=2)[CH2:52][CH2:51][C:50]2([O:49][CH2:48][CH2:47][O:46]2)[CH2:55][CH2:54]1)=[O:58])([CH3:62])[CH3:61]

Komponenten

8

Edukt 4

HCID 7912DiisopropylamineHCID 61028n-Butyl lithiumHCID 58456132HCID 58456132, VerbindungHCID 59733754N-(1,4-dioxaspiro[4.5]dec-8-ylidene)-2-methylpropane-2-sulfinamide

Produkt 1

HCID 67260932HCID 67260932, VerbindungAusbeute 75 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel3×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To diisopropyl amine (318 μL, 2.23 mmol) in tetrahydrofuran (3.7 mL) at 0° C. was added N-butyllithium (2.5 M in hexanes, 892 μL, 2.23 mmol). The mixture was stirred for 15 minutes, then cooled to −78° C. INTERMEDIATE 4 (250 mg, 0.74 mmol) dissolved in tetrahydrofuran (1 mL) was added dropwise over 5 minutes. The mixture was stirred for 30 minutes at −78° C., then the product of Step 1 (212 mg, 0.82 mmol) dissolved in tetrahydrofuran (1 mL) was added dropwise. The reaction mixture was stirred for 2 h, and then quenched with saturated aqueous ammonium chloride, extracted with ethyl acetate (3×), and the combined organic fractions were dried over sodium sulfate, filtered, and concentrated. Purification by column chromatography on silica gel (0:100 to 80:20 ethyl acetate:hexanes gradient, then 0:100 to 15:85 methanol:dichloromethane gradient) afforded 2-methyl-N-{8-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1,4-dioxaspiro[4.5]dec-8-yl}propane-2-sulfinamide (318 mg, 0.40 mmol, 75% yield) as a brown solid. MS ESI: [M+H]+ m/z 596.

Aufarbeitung

  1. additionwas added dropwise over 5 minutes
  2. stirringThe mixture was stirred for 30 minutes at −78° C.
  3. additionwas added dropwise
  4. stirringThe reaction mixture was stirred for 2 h
  5. customquenched with saturated aqueous ammonium chloride
  6. extractionextracted with ethyl acetate (3×)
  7. dry with materialthe combined organic fractions were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by column chromatography on silica gel (0:100 to 80:20 ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-106df1faf92341a4a7505d43f06339fc
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08759366B2

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