Acetic Acid → HCID 10723401, compound

HRID 366240Notes

Reaction equation

HRID 366240 reaction equation
[CH3:1][N:2]([C@@H:12]([C:24](=[O:39])[N:25]([CH3:38])[C@@H:26]([C:34](=[O:37])[NH:35][CH3:36])[CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:13][C:14]1[CH:23]=[CH:22][C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=1)[C:3](=[O:11])/[CH:4]=[CH:5]/[CH2:6][C:7]([NH2:10])([CH3:9])[CH3:8].C(O)(=O)C.[Si:44]([O:51][C@H:52]([CH3:55])[CH:53]=O)([C:47]([CH3:50])([CH3:49])[CH3:48])([CH3:46])[CH3:45].C([BH3-])#N.[Na+]>CO>[Si:44]([O:51][C@H:52]([CH3:55])[CH2:53][NH:10][C:7]([CH3:8])([CH3:9])[CH2:6]/[CH:5]=[CH:4]/[C:3]([N:2]([C@H:12]([CH2:13][C:14]1[CH:23]=[CH:22][C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=1)[C:24]([N:25]([C@H:26]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:34]([NH:35][CH3:36])=[O:37])[CH3:38])=[O:39])[CH3:1])=[O:11])([C:47]([CH3:48])([CH3:49])[CH3:50])([CH3:46])[CH3:45]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydride2×HCID 9810101TabimorelinHCID 10987035(R)-2-(tert-Butyldimethylsilyloxy)propanal

Product 1

HCID 10723401HCID 10723401, compoundYield 23.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

(2E)-5-Amino-5-methylhex-2-enoic acid N-methyl-N-((1R)-1-(N-methyl-N-((1R)-1-(methylcarbamoyl)-2-phenylethyl)carbamoyl)-2-(2-naphthyl)ethyl)amide (318 mg, 0.60 mmol) was dissolved in methanol (20 ml) and glacial acetic acid (0.48 ml, 8.4 mmol). 3 Å mol sieves (9 g) and a solution of (2R)-2-(tert-butyldimethylsilyloxy)propanal (1.33 g, 7.06 mmol) in methanol (10 ml) were added successively. Sodium cyanoborohydride (220 mg, 3.53 mmol) was added as a solid. The reaction mixture was stirred at room temperature for 45 min, before a second batch of sodium cyanoborohydride (220 mg, 3.53 mmol) was added. The reaction mixture was stirred for 16 h at room temperature. The mol sieves was filtered off through a plug of celite. The celite was washed with methanol (200 ml). The solvents of the combined filtrates were removed in vacuo. The residue was dissolved in 1 N sodium hydroxide solution (50 ml) and tert-butyl methyl ether (50 ml). The phases were separated. The aqueous phase was extracted with tert-butyl methyl ether (3×50 ml). The combined organic layers were dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (35 g), using ethyl acetate/heptane/triethylamine (20:10:1) as eluent, to give 99 mg of (2R)-2-(N-((2R)-2-(N-((2E)-5-((2R)-2-(tert-butyldimethylsilyloxy)propylamino)-5-methylhex-2-enoyl)-N-methylamino)-3-(2-naphthyl)propionyl)-N-methylamino)-N-methyl-3-phenylpropionamide.

Workup

  1. additionwas added
  2. filtrationThe mol sieves was filtered off through a plug of celite
  3. washThe celite was washed with methanol (200 ml)
  4. customThe solvents of the combined filtrates were removed in vacuo
  5. dissolutionThe residue was dissolved in 1 N sodium hydroxide solution (50 ml)
  6. customThe phases were separated
  7. extractionThe aqueous phase was extracted with tert-butyl methyl ether (3×50 ml)
  8. dry with materialThe combined organic layers were dried over magnesium sulfate
  9. customThe solvent was removed in vacuo
  10. customThe crude product was purified by flash chromatography on silica (35 g)

Sources & evidence

ORD record
ord-b6707459d8b648619797f11d411e0039
Source dataset
uspto-grants-2000_10
Patent number
US06127391

Reaction notes

Loading…