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 471315Notes

Reaction equation

HRID 471315 reaction equation
[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

Participants

6

Reactant 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

Product 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

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-0aec87363c0a4024ac990fe135204a9d
Source dataset
uspto-grants-2014_01
Patent number
US08629271B2

Reaction notes

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