1,2-Dichloroethane → HCID 54698990, compound

HRID 1453886Notes

Reaction equation

HRID 1453886 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:11][NH:12][C:13]([C:15]2[C:31]([OH:32])=[C:18]3[C:19](=[O:30])[N:20]([CH3:29])[CH2:21][C@H:22]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[N:17]3[N:16]=2)=[O:14])=[C:6]([CH:10]=1)[C:7](O)=[O:8].C1C=[N:37][C:36]2N(O)N=NC=2C=1.C(Cl)CCl.CN.C1COCC1.C(N(CC)CC)C>CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:11][NH:12][C:13]([C:15]2[C:31]([OH:32])=[C:18]3[C:19](=[O:30])[N:20]([CH3:29])[CH2:21][C@H:22]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[N:17]3[N:16]=2)=[O:14])=[C:6]([C:7]([NH:37][CH3:36])=[O:8])[CH:10]=1

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 6329MethylamineHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 181649HOAtHCID 68952640HCID 68952640, compound

Product 1

HCID 54698990HCID 54698990, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-fluoro-2-[({[(7S)-3-hydroxy-5-methyl-4-oxo-7-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl]carbonyl}amino)methyl]benzoic acid (47 mg, 0.106 mmol) in DMF (1 mL) were added HOAT (44 mg, 0.322 mmol), and EDC (62 mg, 0.322 mmol). The reaction mixture was stirred at ambient temperature 15 minutes then 2M methylamine in THF (214 μL, 0.429 mmol) and triethylamine (45 μL, 0.322 mmol) were added. The reaction was stirred at ambient temperature for 5 hours. The crude reaction 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 8.55 (t, J=6.2 Hz, 1H), 8.48 (m, 1H), 7.3-7.4 (m, 4H), 7.25 (m, 2H), 7.03 (m, 2H), 5.75 (t, J=4.0 Hz, 1H), 4.68 (ABX, J=15.2, 6.4 Hz, 2H), 4.18 (dd, J=13.4, 4.6 Hz, 1H), 3.79 (dd, J=13.4, 3.8 Hz, 1H), 2.87 (s, 3H), 2.75 (d, J=4.6 Hz, 3H); HRMS (FT-ICR) C23H22FN5O4+H=452.1735; calculated 452.1729.

Workup

  1. stirringThe reaction was stirred at ambient temperature for 5 hours
  2. customThe crude reaction
  3. customwas 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-4d4aa3f7840340d2a12f24c5bd41b12a
Source dataset
uspto-grants-2009_01
Patent number
US07476666B2

Reaction notes

Loading…