Diisopropylethylamine → tert-butyl 2-(4-fluorophenyl)-3-(4-((S)-5-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate

HRID 625057Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 625057
CCN(C(C)C)C(C)C.Cl.Cl.[CH3:12][C@H:13]1[C:21]2[C:20]([N:22]3[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)=[N:19][CH:18]=[N:17][C:16]=2[CH2:15][S:14]1.[C:28]([O:32][C:33]([N:35]([CH:48]([CH3:50])[CH3:49])[CH2:36][CH:37]([C:41]1[CH:46]=[CH:45][C:44]([F:47])=[CH:43][CH:42]=1)[C:38](O)=[O:39])=[O:34])([CH3:31])([CH3:30])[CH3:29].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>C(Cl)Cl.CCOC(C)=O>[F:47][C:44]1[CH:45]=[CH:46][C:41]([CH:37]([C:38]([N:25]2[CH2:26][CH2:27][N:22]([C:20]3[C:21]4[C@H:13]([CH3:12])[S:14][CH2:15][C:16]=4[N:17]=[CH:18][N:19]=3)[CH2:23][CH2:24]2)=[O:39])[CH2:36][N:35]([CH:48]([CH3:49])[CH3:50])[C:33](=[O:34])[O:32][C:28]([CH3:30])([CH3:29])[CH3:31])=[CH:42][CH:43]=1

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 674576973-(Tert-butoxycarbonyl(isopropyl)amino)-2-(4-fluorophenyl)propanoic acidHCID 67459940HCID 67459940, Verbindung

Produkt 1

HCID 67459971tert-butyl 2-(4-fluorophenyl)-3-(4-((S)-5-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamateAusbeute 72 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

DIPEA (0.089 mL, 0.51 mmol) was added to a stirred suspension of (S)-5-methyl-4-(piperazin-1-yl)-5,7-dihydrothieno[3,4-d]pyrimidine dihydrochloride (40 mg, 0.13 mmol), 3-(tert-butoxycarbonyl(isopropyl)amino)-2-(4-fluorophenyl)propanoic acid (50 mg, 0.15 mmol) and O-(1H-Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (58 mg, 0.15 mmol) in DCM (10 mL) at room temperature. The reaction mixture was stirred at room temperature for 4 hours, diluted with EtOAc, washed with saturated aqueous bicarbonate and then 1N HCl. The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The residue was purified by silica gel chromatography (75% EtOAc/hexanes) to give tert-butyl 2-(4-fluorophenyl)-3-(4-((S)-5-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate (50 mg, 72% yield) as a mixture of 2 diastereomers. LCMS (APCI+) [M-Boc+H]+ 444.

Aufarbeitung

  1. washwashed with saturated aqueous bicarbonate
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by silica gel chromatography (75% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-1a216a1c2438478ca1d7109c7cf0e986
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09303040B2

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