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

HRID 1689469Notes

Reaction equation

HRID 1689469 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][C:31]([CH3:35])([CH3:34])[CH:32]=O)[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.[NH2:40][CH2:41][C@@H:42]([C:44]1[C:52]2[S:51][C:50](=[O:53])[NH:49][C:48]=2[C:47]([OH:54])=[CH:46][CH:45]=1)[OH:43].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[CH:1]([OH:4])=[O:3].[OH:54][C:47]1[C:48]2[NH:49][C:50](=[O:53])[S:51][C:52]=2[C:44]([C@@H:42]([OH:43])[CH2:41][NH:40][CH2:35][C:31]([CH3:32])([CH3:34])[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]([CH3:7])[CH3:6])[S:9][CH:10]=4)=[O:14])[CH2:20]3)[CH2:25][CH2:24]2)=[CH:45][CH:46]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 579890537-(4-(2-Isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2,2-dimethylheptanalHCID 671669747-[(1R)-2-Amino-1-hydroxy-ethyl]-4-hydroxy-3H-benzothiazol-2-one, acetate salt

Product 1

HCID 67292882(R)-4-Hydroxy-7-(1-hydroxy-2-(7-(4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2,2-dimethylheptylamino)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 7-(4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2,2-dimethylheptanal (example 102, step d) (0.33 g) and (R)-7-(2-amino-1-hydroxyethyl)-4-hydroxybenzo[d]thiazol-2(3H)-one hydrochloride (WO2007027134, example 1, step d) (0.25 g) with 3 Å molecular sieves in anhydrous methanol (10 mL). The mixture was stirred for 5 min then cooled to 0° C. Sodium triacetoxyborohydride (0.13 g) was added and the resulting mixture stirred at RT for 16.5 h. The solution was filtered then concentrated in vacuo. The residue was dissolved in a mixture of acetonitrile and water and purified 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 give the titled compound as a white solid. Yield 0.1 g.

Workup

  1. stirringthe resulting mixture stirred at RT for 16.5 h
  2. filtrationThe solution was filtered
  3. concentrationthen concentrated in vacuo
  4. dissolutionThe residue was dissolved in a mixture of acetonitrile and water
  5. custompurified by preparative HPLC (Phenomenex Gemini®, Gradient: 10-40% acetonitrile in 0.1% aqueous formic acid)
  6. additionThe fractions containing product
  7. customfreeze-dried

Sources & evidence

ORD record
ord-7507742ed9ef4a78a2a0c3a5330290ee
Source dataset
uspto-grants-2012_04
Patent number
US08148373B2

Reaction notes

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