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 1689543ノート

反応式

HRID 1689543 の反応式
[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

参加物

6

反応物 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

生成物 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

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
0 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-0e308bb036424954997d0014eb61c4dc
出典データセット
uspto-grants-2012_04
特許番号
US08148373B2

反応ノート

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