1,2-Dichloroethane → HCID 68951430, compound

HRID 1453884Notes

Reaction equation

HRID 1453884 reaction equation
[OH:1][C:2]1[C:3]([C:19]([OH:21])=O)=[N:4][N:5]2[C@@H:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH2:9][N:8]([CH3:17])[C:7](=[O:18])[C:6]=12.C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl.Cl.[NH2:37][CH2:38][C:39]1[CH:48]=[CH:47][C:46]([F:49])=[CH:45][C:40]=1[C:41]([O:43][CH3:44])=[O:42].C(N(CC)CC)C>CN(C=O)C>[F:49][C:46]1[CH:47]=[CH:48][C:39]([CH2:38][NH:37][C:19]([C:3]2[C:2]([OH:1])=[C:6]3[C:7](=[O:18])[N:8]([CH3:17])[CH2:9][C@H:10]([C:11]4[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=4)[N:5]3[N:4]=2)=[O:21])=[C:40]([CH:45]=1)[C:41]([O:43][CH3:44])=[O:42]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 181649HOAtHCID 67234729HCID 67234729, compoundHCID 68952351HCID 68952351, compound

Product 1

HCID 68951430HCID 68951430, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (7S)-3-hydroxy-5-methyl-4-oxo-7-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxylic acid (246 mg, 0.856 mmol) in DMF (3 mL) were added HOAT (175 mg, 1.28 mmol), and EDC (246 mg, 1.28 mmol). The reaction mixture was stirred at ambient temperature 15 minutes then methyl 2-(aminomethyl)-5-fluorobenzoate hydrochloride (226 mg, 1.03 mmol) and triethylamine (0.13 g, 1.28 mmol) were added. The reaction was stirred at ambient temperature overnight. The solvent was removed in vacuo, and the resulting residue was purified by reverse phase chromatography on a C-18 column using a gradient elution of 95-5% H2O (0.1% TFA)/CH3CN (0.1% TFA). Collection and concentration of the appropriate fractions afforded the product as a light pink solid. 1H NMR (400 MHz, d6-DMSO) δ 9.60 (bs, 1H), 8.60 (t, J=6.2 Hz, 1H), 7.61 (dd, J=9.5, 2.3 Hz, 1H), 7.45 (m, 2H), 7.36 (m, 3H), 7.04 (d, J=7.1 Hz, 2H), 5.75 (t, J=4.0 Hz, 1H), 4.68 (ABX, J=15.8, 6.2 Hz, 2H), 4.18 (dd, J=13.4, 4.5 Hz, 1H), 3.86 (s, 3H), 3.81 (dd, J=13.4, 4.0 Hz, 1H), 2.88 (s, 3H); ES MS (M+1)-453.

Workup

  1. stirringThe reaction was stirred at ambient temperature overnight
  2. customThe solvent was removed in vacuo
  3. customthe resulting residue was purified by reverse phase chromatography on a C-18 column
  4. washa gradient elution of 95-5% H2O (0.1% TFA)/CH3CN (0.1% TFA)
  5. customCollection and concentration of the appropriate fractions

Sources & evidence

ORD record
ord-5c2b5ece49c74a99b4426b062eb58aaf
Source dataset
uspto-grants-2009_01
Patent number
US07476666B2

Reaction notes

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