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

HRID 625036Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 625036
Cl.Cl.[CH3:3][C@H:4]1[C:12]2[C:11]([N:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)=[N:10][CH:9]=[N:8][C:7]=2[CH2:6][S:5]1.[C:19]([O:23][C:24]([N:26]([CH:39]([CH3:41])[CH3:40])[CH2:27][CH:28]([C:32]1[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=1)[C:29](O)=[O:30])=[O:25])([CH3:22])([CH3:21])[CH3:20].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>C(Cl)Cl>[Cl:38][C:35]1[CH:36]=[CH:37][C:32]([CH:28]([C:29]([N:16]2[CH2:17][CH2:18][N:13]([C:11]3[C:12]4[C@H:4]([CH3:3])[S:5][CH2:6][C:7]=4[N:8]=[CH:9][N:10]=3)[CH2:14][CH2:15]2)=[O:30])[CH2:27][N:26]([CH:39]([CH3:40])[CH3:41])[C:24](=[O:25])[O:23][C:19]([CH3:21])([CH3:20])[CH3:22])=[CH:33][CH:34]=1

Komponenten

6

Edukt 4

HCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 251786973-{[(tert-Butoxy)carbonyl](propan-2-yl)amino}-2-(4-chlorophenyl)propanoic acidHCID 67459940HCID 67459940, Verbindung

Produkt 1

HCID 67457700tert-butyl 2-(4-chlorophenyl)-3-(4-((S)-5-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamateAusbeute 70 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of (S)-5-methyl-4-(piperazin-1-yl)-5,7-dihydrothieno[3,4-d]pyrimidine dihydrochloride (0.5 g, 1.62 mmol) and 3-(tert-butoxycarbonyl(isopropyl)amino)-2-(4-chlorophenyl)propanoic acid (0.7 g, 2.05 mmol) in DCM (40 mL) were added HBTU (1.0 g, 2.64 mmol) and triethylamine (1.38 mL, 9.88 mL). The mixture was stirred at room temperature for 1 hour. The solvent was removed, and the residue was dissolved in ethyl acetate (200 mL) and washed with brine (5×100 mL) and water (3×100 mL). The organic phase was dried and concentrated. The residue was purified by silica gel chromatography, eluting with Hexane/ethyl acetate (2:1-0:1) to give tert-butyl 2-(4-chlorophenyl)-3-(4-((S)-5-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate (0.63 g, 70%). 1H NMR (CDCl3, 400 MHz) δ 8.50 (d, J=5.6 Hz, 1H), 7.31-7.23 (m, 4H), 4.76 (m, 1H), 4.18 (m, 3H), 4.92-3.25 (m, 10H), 1.48 (m, 12H), 0.99 (m, 3H), 0.69 (m, 3H). MS (APCI+) [M+H]+ 561.

Aufarbeitung

  1. customThe solvent was removed
  2. dissolutionthe residue was dissolved in ethyl acetate (200 mL)
  3. washwashed with brine (5×100 mL) and water (3×100 mL)
  4. customThe organic phase was dried
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with Hexane/ethyl acetate (2:1-0:1)

Quellen und Nachweise

ORD-Eintrag
ord-e77f8db908a94252b4885bf54404c617
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09303040B2

Notizen zur Reaktion

Wird geladen…