1,2-Dichloroethane → 3-Benzyloxy-2-[4-fluorobenzyl(methyl)aminocarbonyl]-5-methyl-4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine

HRID 1453857Notes

Reaction equation

HRID 1453857 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([C:20](O)=[O:21])=[N:11][N:12]2[CH2:17][CH2:16][N:15]([CH3:18])[C:14](=[O:19])[C:13]=12)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[F:37][C:38]1[CH:46]=[CH:45][C:41]([CH2:42][NH:43][CH3:44])=[CH:40][CH:39]=1>CN(C=O)C>[CH2:1]([O:8][C:9]1[C:10]([C:20]([N:43]([CH2:42][C:41]2[CH:45]=[CH:46][C:38]([F:37])=[CH:39][CH:40]=2)[CH3:44])=[O:21])=[N:11][N:12]2[CH2:17][CH2:16][N:15]([CH3:18])[C:14](=[O:19])[C:13]=12)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 7368601-(4-fluorophenyl)-N-methylmethanamineHCID 68951325HCID 68951325, compound

Product 1

HCID 689514493-Benzyloxy-2-[4-fluorobenzyl(methyl)aminocarbonyl]-5-methyl-4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-benzyloxy-5-methyl-4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxylic acid (50 mg, 0.166 mmol) in DMF (2 mL) were added EDC (32 mg, 0.166 mmol), HOBT (27 mg, 0.199 mmol), and 4-fluoro-N-methylbenzylamine (23 mg, 0.166 mmol). The reaction was stirred at room temperature overnight and partitioned between EtOAc and brine. The aqueous layer was extracted several times with EtOAc, and the combined organic extracts were dried over Na2SO4 and concentrated in vacuo. Purification by reverse phase chromatography on a C-18 column using a gradient elution of 95-5% H2O (0.1% TFA)/CH3CN (0.1% TFA) and collection and concentration of the appropriate fractions afforded the title product. 1H NMR (400 MHz, CDCl3) δ 7.44-7.42 (m, 1H), 7.38-7.29 (m, 4H), 7.16-7.12 (m, 1H), 6.98-6.92 (m, 3H), 5.30-5.24 (m, 4H), 4.39-4.34 (m, 2H), 3.80-3.73 (m, 2H), 3.19-3.17 (d, 3H), 2.89-2.86 (d, 3H); ES MS (M+1)=423.

Workup

  1. custompartitioned between EtOAc and brine
  2. extractionThe aqueous layer was extracted several times with EtOAc
  3. dry with materialthe combined organic extracts were dried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customPurification by reverse phase chromatography on a C-18 column
  6. washa gradient elution of 95-5% H2O (0.1% TFA)/CH3CN (0.1% TFA) and collection and concentration of the appropriate fractions

Sources & evidence

ORD record
ord-cb87a3ec7550436d9f172cb927926ad9
Source dataset
uspto-grants-2009_01
Patent number
US07476666B2

Reaction notes

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