Acetic Acid → 1-[[4-[[4-[2-[[(2R)-2-Hydroxy-2-[4-hydroxy[(methylsulfonyl)amino]phenyl]ethyl]amino]ethyl]phenyl]amino]-1-piperidinyl]carbonyl]-L-proline, Methyl Ester

HRID 1281580

Reaction equation

HRID 1281580 reaction equation
CO[CH:3](OC)[CH2:4][C:5]1[CH:28]=[CH:27][C:8]([NH:9][CH:10]2[CH2:15][CH2:14][N:13]([C:16]([N:18]3[CH2:22][CH2:21][CH2:20][C@H:19]3[C:23]([O:25][CH3:26])=[O:24])=[O:17])[CH2:12][CH2:11]2)=[CH:7][CH:6]=1.[I-].[Na+].Cl[Si](Cl)(Cl)C.[C:38](O)(=[O:40])C.NC[C@@H]([C:46]1[CH:47]=[CH:48][C:49](O)=[C:50]([NH:52][S:53]([CH3:56])(=[O:55])=[O:54])[CH:51]=1)O.[C:58]([BH3-])#[N:59].[Na+].C[OH:63]>C(#N)C.ClCCl>[OH:40][C@H:38]([C:49]1[CH:48]=[CH:47][C:46]([OH:63])=[CH:51][C:50]=1[NH:52][S:53]([CH3:56])(=[O:54])=[O:55])[CH2:58][NH:59][CH2:3][CH2:4][C:5]1[CH:28]=[CH:27][C:8]([NH:9][CH:10]2[CH2:11][CH2:12][N:13]([C:16]([N:18]3[CH2:22][CH2:21][CH2:20][C@H:19]3[C:23]([O:25][CH3:26])=[O:24])=[O:17])[CH2:14][CH2:15]2)=[CH:7][CH:6]=1

Participants

10

Reactant 7

HCID 176Acetic AcidHCID 887MethanolHCID 5238Sodium IodideHCID 6399TrichloromethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 12047933(R)-N-(5-(2-amino-1-hydroxyethyl)-2-hydroxyphenyl)methanesulfonamideHCID 90751503Methyl (2S)-1-({4-[4-(2,2-dimethoxyethyl)anilino]-1-piperidinyl)carbonyl)-2-pyrrolidinecarboxylate

Product 1

HCID 1317234961-[[4-[[4-[2-[[(2R)-2-Hydroxy-2-[4-hydroxy[(methylsulfonyl)amino]phenyl]ethyl]amino]ethyl]phenyl]amino]-1-piperidinyl]carbonyl]-L-proline, Methyl Ester

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

Methyl (2S)-1-({4-[4-(2,2-dimethoxyethyl)anilino]-1-piperidinyl}carbonyl)-2-pyrrolidinecarboxylate (1.0 g, 2.38 mmol) was added to a pre-prepared mixture of sodium iodide (0.837 g, 5.58 mmol) and trichloro(methyl)silane (0.525 mL, 4.46 mmol) in anhydrous acetonitrile. The reaction was stirred at ambient temperature for 10 minutes. Dichloromethane was added and the reaction washed with 10% sodium thiosulfate solution, water and brine. The organic layer was dried over anhydrous magnesium sulfate, filtered and the solvent partially removed in vacuo. The aldehyde solution was used directly and treated with methanol, acetic acid (0.146 mL, 2.43 mmol), N-{5-[(1R)-2-amino-1-hydroxyethyl]-2-hydroxyphenyl}methanesulfonamide (0.55 g, 2.23 mmol) followed by sodium cyanoborohydride (0.154 g, 2.24 mmol). The reaction was stirred at ambient temperature for 24 hours. The reaction was taken to dryness in vacuo, adsorbed onto silica and purified by flash chromatography on silica gel Merck-60 (eluant: 5:1 chloroform-methanol containing 1% ammonium hydroxide) to yield the title compound (0.05 g, 0.083 mmol).

Workup

  1. washthe reaction washed with 10% sodium thiosulfate solution, water and brine
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. customthe solvent partially removed in vacuo
  5. stirringThe reaction was stirred at ambient temperature for 24 hours
  6. custompurified by flash chromatography on silica gel Merck-60 (eluant: 5:1 chloroform-methanol containing 1% ammonium hydroxide)

Sources & evidence

ORD record
ord-6bc4f921679843e9acc2bfa2af96d029
Source dataset
uspto-grants-2002_09
Patent number
US06451814B1

Linked notes

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