Phosphate → (5R)-3-[6-(2-[({3-[(2,3-Dihydroimidazo[2,1-b][1,3]thiazol-6-ylmethyl)amino]-phenyl}methyl)oxy]ethoxy)hexyl]-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one

HRID 219035Notes

Reaction equation

HRID 219035 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH2:8][O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][N:19]2[CH2:23][C@@H:22]([C:24]3[CH:35]=[CH:34][C:27]4[O:28][C:29]([CH3:33])([CH3:32])[O:30][CH2:31][C:26]=4[CH:25]=3)[O:21][C:20]2=[O:36])[CH:5]=[CH:6][CH:7]=1.[S:37]1[CH2:41][CH2:40][N:39]2[CH:42]=[C:43]([CH:45]=O)[N:44]=[C:38]12.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].P([O-])([O-])([O-])=O>ClCCl>[S:37]1[CH2:41][CH2:40][N:39]2[CH:42]=[C:43]([CH2:45][NH:1][C:2]3[CH:3]=[C:4]([CH2:8][O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][N:19]4[CH2:23][C@@H:22]([C:24]5[CH:35]=[CH:34][C:27]6[O:28][C:29]([CH3:32])([CH3:33])[O:30][CH2:31][C:26]=6[CH:25]=5)[O:21][C:20]4=[O:36])[CH:5]=[CH:6][CH:7]=3)[N:44]=[C:38]12

Participants

6

Reactant 4

HCID 1061PhosphateHCID 5049666Sodium triacetoxyborohydrideHCID 112406042,3-Dihydroimidazo[2,1-b][1,3]thiazole-6-carbaldehydeHCID 46833388(5R)-3-{6-[2-{[(3-aminophenyl)methyl]oxy}ethoxy]hexyl}-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one

Product 1

HCID 66845391(5R)-3-[6-(2-[({3-[(2,3-Dihydroimidazo[2,1-b][1,3]thiazol-6-ylmethyl)amino]-phenyl}methyl)oxy]ethoxy)hexyl]-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-oneYield 67.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (5R)-3-{6-[2-{[(3-aminophenyl)methyl]oxy}ethoxy]hexyl}-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one (200 mg) and 2,3-dihydroimidazo[2,1-b][1,3]thiazole-6-carboxaldehyde (62 mg) (WO94/10178) in dichloromethane (10 ml) was treated under nitrogen with sodium triacetoxy borohydride (340 mg) and stirred at 20° for 1.5 h. The mixture was cooled to 0°, phosphate buffer solution (pH6.5, 20 ml) was added and the mixture was extracted with EtOAc (3×30 ml). The combined organic extracts were dried (Na2SO4) and the solvent evaporated in vacuo to give a residue which was purified by SPE. Elution with dichloromethane, dichloromethane-EtOH-ammonia (400:8:1) then (225:8:1) gave the title compound (172 mg). LCMS RT=3.16 min, ES+ve 637 (MH)+.

Workup

  1. temperatureThe mixture was cooled to 0°
  2. extractionthe mixture was extracted with EtOAc (3×30 ml)
  3. dry with materialThe combined organic extracts were dried (Na2SO4)
  4. customthe solvent evaporated in vacuo
  5. customto give a residue which
  6. customwas purified by SPE
  7. washElution with dichloromethane, dichloromethane-EtOH-ammonia (400:8:1)

Sources & evidence

ORD record
ord-f61379ab51c2411c8cd0dbb0d6745d90
Source dataset
uspto-grants-2012_06
Patent number
US08198483B2

Reaction notes

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