Diisopropylamine → HCID 67260932, Verbindung

HRID 1040214Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1040214
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 21), 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 21), and
  5. customthen quenched 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-6d5ab8ec5ffb4ca6ba9b2a12bc3e8ecf
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08551984B2

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