Pyridine → HCID 58017531, compound

HRID 1642759Notes

Reaction equation

HRID 1642759 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:28]2[CH:32]=[N:31][N:30]=[N:29]2)=[C:6]([CH:27]=1)[CH2:7][NH:8][C:9]([C@H:11]1[N:15]([C:16](=[O:26])[C@@H:17]([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)[OH:18])[N:14]=[CH:13][CH2:12]1)=[O:10].N1C=CC=CC=1.[C:39](OC(=O)C)(=[O:41])[CH3:40]>ClCCl.CN(C1C=CN=CC=1)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:28]2[CH:32]=[N:31][N:30]=[N:29]2)=[C:6]([CH2:7][NH:8][C:9]([C@H:11]2[N:15]([C:16](=[O:26])[C@H:17]([O:18][C:39](=[O:41])[CH3:40])[C:19]3[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=3)[N:14]=[CH:13][CH2:12]2)=[O:10])[CH:27]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 7918Acetic Anhydride2×HCID 44537923(5S)-N-[5-Chloro-2-(1H-tetrazol-1-yl)benzyl]-1-[(2R)-2-(4-fluorophenyl)-2-hydroxyacetyl]-4,5-dihydro-1H-pyrazole-5-carboxamide

Product 1

HCID 58017531HCID 58017531, compoundYield 90.7%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To (5S)—N-[5-chloro-2-(1H-tetrazol-1-yl)benzyl]-1-[(2R)-2-(4-fluorophenyl)-2-hydroxyacetyl]-4,5-dihydro-1H-pyrazole-5-carboxamide (Example 1) (483 mg, 1.05 mmol) in dichloromethane (10 mL) was added pyridine (2 mL) and acetic anhydride (100 μL, 1.06 mmol). The mixture was stirred for 4 h. Another portion of acetic anhydride (600 μL, 6.34 mmol) and DMAP (23 mg, 0.19 mmol) was added and the mixture was stirred for another 15 h. The solvents were removed by evaporation and the residue was purified by HPLC (MeCN gradient 0 to 100% in aqueous 0.1 M NH4OAc buffer containing 5% MeCN, C8 column: 50×300 mm). The relevant fractions were collected, combined and freeze dried to give the title compound (476 mg, 90%) as a solid material.

Workup

  1. stirringthe mixture was stirred for another 15 h
  2. customThe solvents were removed by evaporation
  3. customthe residue was purified by HPLC (MeCN gradient 0 to 100% in aqueous 0.1 M NH4OAc buffer containing 5% MeCN, C8 column: 50×300 mm)
  4. customThe relevant fractions were collected
  5. customfreeze dried

Sources & evidence

ORD record
ord-f81735a1753e4879bd8bdc131db3abd5
Source dataset
uspto-grants-2012_02
Patent number
US08119673B2

Reaction notes

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