Sodium Bicarbonate → HCID 11671436, compound

HRID 1158364Notes

Reaction equation

HRID 1158364 reaction equation
C(OC([N:8]1[CH2:12][C@@H:11]([CH2:13][N:14]([CH:31]([CH3:33])[CH3:32])[C:15](=[O:30])[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH2:25][CH2:26][CH2:27][O:28][CH3:29])[CH:17]=2)[C@H:10]([CH2:34][N:35]([C:39](=[O:48])[CH2:40][C:41]([NH:44][C:45](=[O:47])[CH3:46])([CH3:43])[CH3:42])[CH:36]2[CH2:38][CH2:37]2)[CH2:9]1)=O)(C)(C)C.C([O-])(O)=O.[Na+]>ClCCCl.[Zn+2].[Br-].[Br-]>[C:45]([NH:44][C:41]([CH3:42])([CH3:43])[CH2:40][C:39]([N:35]([CH2:34][C@@H:10]1[CH2:9][NH:8][CH2:12][C@H:11]1[CH2:13][N:14]([CH:31]([CH3:32])[CH3:33])[C:15](=[O:30])[C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH2:25][CH2:26][CH2:27][O:28][CH3:29])[CH:17]=1)[CH:36]1[CH2:38][CH2:37]1)=[O:48])(=[O:47])[CH3:46]

Participants

5

Reactant 2

HCID 516892Sodium BicarbonateHCID 68642832HCID 68642832, compound

Product 1

HCID 11671436HCID 11671436, compound

Reagents, catalysts & solvents 2

HCID 10421208Zinc bromideCatalyst2×HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
55 °C

Procedure

ZnBr2 (110 mg, 0.49 mmol) is added to a solution of (3R,4R)-3-{[(3-acetylamino-3-methyl-butyryl)-cyclopropyl-amino]-methyl}-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (150 mg, 0.22 mmol) in 1,2-dichloroethane (5 mL) and the resulting suspension is stirred at 55° C. for 16 h. In order to drive the reaction to completion another portion of ZnBr2 (50 mg, 0.22 mmol) is added and heating is continued for another 24 h. For workup a sat. solution of NaHCO3 is added and the mixture is extracted with CH2Cl2. Drying (Na2SO4) of the combined extracts, filtration and evaporation of the solvent affords the desired product as free base. The free base is dissolved in dioxane (2 mL) and fumaric acid (11 mg, 0.11 mmol) is added. Lyophilization yields the title compound as hemifumarate salt. MS (LC-MS): 575.0 [M+H]+; tR (HPLC, Macherey-Nagel Nucleosil C18 column, 10-100% CH3CN/H2O/5 min, 100% CH3CN/3 min, CH3CN and H2O containing 0.1% TFA, flow: 1.5 mL/min): 4.90 min.

Workup

  1. additionis added
  2. temperatureheating
  3. waitis continued for another 24 h
  4. extractionthe mixture is extracted with CH2Cl2
  5. customDrying
  6. filtration(Na2SO4) of the combined extracts, filtration and evaporation of the solvent

Sources & evidence

ORD record
ord-d6e9bbdf417f482bb3f0a6c770b7626a
Source dataset
uspto-grants-2010_10
Patent number
US07807709B2

Reaction notes

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