Triethylamine → Phenylmethyl [4-[[[5-(dimethylamino)-1-naphthalenyl]sulfonyl]amino]-5-[4-ethyl-1-piperidinyl]-5-oxopentyl]carbamate

HRID 6368

Reaktionsgleichung

Reaktionsgleichung von HRID 6368
[CH3:1][N:2]([CH3:35])[C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH:5]=[CH:6][CH:7]=[C:8]2[S:13]([NH:16][CH:17]([CH2:21][CH2:22][CH2:23][NH:24][C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26])[C:18](O)=[O:19])(=[O:15])=[O:14].C(N(CC)CC)C.[CH2:43]([CH:45]1[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]1)[CH3:44].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1>CN(C)C=O>[CH3:35][N:2]([CH3:1])[C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH:5]=[CH:6][CH:7]=[C:8]2[S:13]([NH:16][CH:17]([C:18]([N:48]1[CH2:49][CH2:50][CH:45]([CH2:43][CH3:44])[CH2:46][CH2:47]1)=[O:19])[CH2:21][CH2:22][CH2:23][NH:24][C:25](=[O:26])[O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)(=[O:15])=[O:14]

Komponenten

6

Edukt 4

HCID 8471TriethylamineHCID 767044-EthylpiperidineHCID 199401P,P-Diphenylphosphinic azideHCID 197931492-[[[5-(Dimethylamino)-1-naphthalenyl]sulfonyl]amino]-5-[[(phenylmethoxy)carbonyl]amino]pentanoic acid

Produkt 1

HCID 54192395Phenylmethyl [4-[[[5-(dimethylamino)-1-naphthalenyl]sulfonyl]amino]-5-[4-ethyl-1-piperidinyl]-5-oxopentyl]carbamateAusbeute 91,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a cold (0° C.), nitrogen-blanketed mixture of 2d (48.90 g, 0.098 mol), triethylamine (25.0 mL, 0.18 mol) and 4-ethylpiperidine (20.0 g, 0.18 mol) in anhydrous dimethylformamide (160 mL) was added dropwise diphenylphosphoryl azide (21.1 mL, 0.098 mol). The mixture was stirred at about 0° C. for about 1 hour and at ambient temperature for about 2 hours before it was partitioned between ether (150 mL) and water (80 mL). The ethereal layer was separated and the aqueous layer was extracted four additional times with ether (80 mL). The combined ethereal extracts were then washed with saturated sodium bicarbonate solution and brine prior to drying (Na2SO4) and solvent concentration. Two identical reactions were performed in tandem. Purification of the combined residues by HPLC on silica gel (elution with 50% ethyl acetate in hexane) furnished 53.09 g (45%) of 3d as a yellow foam, m.p. 56°-62° C. (dec.); 1H NMR (CDCl3) δ 8.47 (d, 1H), 8.30 (t, 1H), 8.16 (d, 1H), 7.58 (m, 1H), 7.56-7.36 (m, 6H), 7.15 (d, 1H), 6.17-5.96 (dd, 1H), 5.10 (s, 2H), 4.75-4.62 (bm, 1H), 4.10-3.91 (bm, 2H), 3.42-3.30 (bm, 1H), 3.16-2.92 (bm, 2H), 2.85-2.83 (d, 6H), 2.68-2.41 (dt, 1H), 2.24-1.97 (m, 1H), 1.57-0.76 (m, 3 H), 0.16-0.08 (m, 1H); 13C NMR (CDCl3) ppm 168.50, 156.40, 151.62, 136.50, 135.00, 134.70, 130.56, 130.44, 129.80, 129.35, 129.18, 128.50, 128.41, 128.07, 128.00, 123.01, 122.93, 119.33, 115.58, 115.47, 66.60, 52.29, 52.19, 45.70, 45.43, 45.37, 45.13, 42.02, 42.21, 40.35, 40.18, 37.48, 37.34, 32.17, 31.92, 31.06, 30.79, 30.65, 29.67, 28.77, 28.58, 25.12, 11.08; IR (KBR, cm-1) 33,50 2975, 2975, 2950, 1725, 1650, 1550, 1475, 1350, 1275, 1180, 1160; MS m/z (MH+) 595.

Aufarbeitung

  1. customwas partitioned between ether (150 mL) and water (80 mL)
  2. customThe ethereal layer was separated
  3. extractionthe aqueous layer was extracted four additional times with ether (80 mL)
  4. washThe combined ethereal extracts were then washed with saturated sodium bicarbonate solution and brine
  5. customto drying
  6. concentration(Na2SO4) and solvent concentration
  7. customPurification of the combined residues by HPLC on silica gel (elution with 50% ethyl acetate in hexane)

Quellen und Nachweise

ORD-Eintrag
ord-2d1677a7d55446d6936250ae86c5bfcb
Quelldatensatz
uspto-grants-1993_09
Patentnummer
US05248673

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