Acetic Acid → (R)-4-Hydroxy-7-(1-hydroxy-2-(10-(4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)decan-2-ylamino)ethyl)benzo[d]thiazol-2(3H)-one formate

HRID 471315Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 471315
[C:1]([OH:4])(=[O:3])C.[CH:5]([C:8]1[S:9][CH:10]=[C:11]([C:13]([N:15]2[CH2:20][C:19]3([CH2:25][CH2:24][N:23]([CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][C:34](=O)[CH3:35])[CH2:22][CH2:21]3)[O:18][CH2:17][CH2:16]2)=[O:14])[N:12]=1)([CH3:7])[CH3:6].C(O)(=O)C.[NH2:41][CH2:42][C@@H:43]([C:45]1[C:53]2[S:52][C:51](=[O:54])[NH:50][C:49]=2[C:48]([OH:55])=[CH:47][CH:46]=1)[OH:44].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[CH:1]([OH:4])=[O:3].[OH:55][C:48]1[C:49]2[NH:50][C:51](=[O:54])[S:52][C:53]=2[C:45]([C@@H:43]([OH:44])[CH2:42][NH:41][CH:34]([CH2:33][CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][N:23]2[CH2:22][CH2:21][C:19]3([O:18][CH2:17][CH2:16][N:15]([C:13]([C:11]4[N:12]=[C:8]([CH:5]([CH3:6])[CH3:7])[S:9][CH:10]=4)=[O:14])[CH2:20]3)[CH2:25][CH2:24]2)[CH3:35])=[CH:46][CH:47]=1

Komponenten

6

Edukt 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 5798891310-(4-(2-Isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)decan-2-oneHCID 671669747-[(1R)-2-Amino-1-hydroxy-ethyl]-4-hydroxy-3H-benzothiazol-2-one, acetate salt

Produkt 1

HCID 67292709(R)-4-Hydroxy-7-(1-hydroxy-2-(10-(4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)decan-2-ylamino)ethyl)benzo[d]thiazol-2(3H)-one formate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Acetic acid (0.053 mL) was added to a mixture of 10-(4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)decan-2-one (example 280, step c) (335 mg) and (R)-7-(2-amino-1-hydroxyethyl)-4-hydroxybenzo[d]thiazol-2(3H)-one hydrochloride (WO2007027134, example 1, step d) (243 mg) in dry methanol with 3 Å molecular sieves at room temperature under nitrogen and stirred for 5 minutes. The mixture was cooled to 0° C. and sodium triacetoxyborohydride (131 mg) was added. The reaction mixture was stirred, warming to room temperature overnight. The mixture was filtered and evaporated. Purification was by preparative HPLC (Phenomenex Gemini®, Gradient: 10-40% acetonitrile in 0.1% aqueous formic acid). The fractions containing product were combined and freeze-dried to afford the titled compound as a white solid. Yield 0.032 g.

Aufarbeitung

  1. stirringThe reaction mixture was stirred
  2. temperaturewarming to room temperature overnight
  3. filtrationThe mixture was filtered
  4. customevaporated
  5. customPurification
  6. additionThe fractions containing product
  7. customfreeze-dried

Quellen und Nachweise

ORD-Eintrag
ord-0aec87363c0a4024ac990fe135204a9d
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08629271B2

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