Diisopropylethylamine → (+/-)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [2-[1,4']bipiperidinyl-1'-yl-1-(7-methyl-1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amide

HRID 2250174Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2250174
[CH3:1][C:2]1[CH:3]=[C:4]([CH2:11][CH:12]([NH:16][C:17]([N:19]2[CH2:24][CH2:23][CH:22]([N:25]3[CH2:34][C:33]4[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=4)[NH:27][C:26]3=[O:35])[CH2:21][CH2:20]2)=[O:18])[C:13](O)=[O:14])[CH:5]=[C:6]2[C:10]=1[NH:9][N:8]=[CH:7]2.[CH:36]([N:39]([CH:42]([CH3:44])[CH3:43])[CH2:40][CH3:41])([CH3:38])C.C1[CH2:49][N:48]([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)[CH2:47]C1.F[P-](F)(F)(F)(F)F.[CH3:78]N(C)C=O.C(Cl)Cl>>[N:39]1([CH:42]2[CH2:43][CH2:49][N:48]([C:13](=[O:14])[CH:12]([NH:16][C:17]([N:19]3[CH2:24][CH2:23][CH:22]([N:25]4[CH2:34][C:33]5[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=5)[NH:27][C:26]4=[O:35])[CH2:21][CH2:20]3)=[O:18])[CH2:11][C:4]3[CH:5]=[C:6]4[C:10](=[C:2]([CH3:1])[CH:3]=3)[NH:9][N:8]=[CH:7]4)[CH2:47][CH2:44]2)[CH2:36][CH2:38][CH2:78][CH2:41][CH2:40]1

Komponenten

5

Edukt 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 21102025(+)-3-(7-methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acidHCID 22350042dichloromethane N,N-dimethylformamide

Produkt 1

HCID 10077700(+/-)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [2-[1,4']bipiperidinyl-1'-yl-1-(7-methyl-1H-indazol-5-ylmethyl)-2-oxo-ethyl]-amideAusbeute 93 %

Versuchsvorschrift

A stirred solution of (±)-3-(7-methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid (65.7 mg, 0.138 mmol) in 2:1 dimethylformamide/methylene chloride (1.5 mL) at 0° C. was treated with 4-(1-piperidyl)-piperidne (46.5 mg, 2 equiv), diisopropylethylamine (0.048 mL, 2 equiv) and PyBOP® (75.5 mg, 1.05 equiv). The ice bath was allowed to melt and the mixture was stirred at room temperature overnight. The solvents were removed under high vacuum and the residue was purified by flash chromatography on silica gel, eluting with 18:1 methylene chloride/methanol containing 1% triethylamine, to give the product as a pale-yellow solid (80.4 mg, 93%). 1H-NMR (CD3OD, 500 MHz) δ −0.28 (1H, m), 0.75 (1H, m), 1.2-2.0 (12H, m), 2.08 (2H, m), 2.4-2.5 (3H, m), 2.59 (3H, s), 2.68 (2H, m), 2.90 (4H, m), 3.08 (4H, m), 3.9-5.1 (4H, several m), 6.81 (1H, d), 6.96 (1H, t), 7.16 (3H, m), 7.49 (1H, s), 8.03 (1H, s). Mass spec.: 627.29 (MH)+.

Aufarbeitung

  1. customThe solvents were removed under high vacuum
  2. customthe residue was purified by flash chromatography on silica gel
  3. washeluting with 18:1 methylene chloride/methanol containing 1% triethylamine

Quellen und Nachweise

ORD-Eintrag
ord-562e347e48894374ba0393880620e58d
Quelldatensatz
uspto-grants-2008_01
Patentnummer
US07314883B2

Notizen zur Reaktion

Wird geladen…