1,2-Dichloroethane → HCID 58504345, compound

HRID 1941894Notes

Reaction equation

HRID 1941894 reaction equation
[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:5]=[CH:4][C:3]=1[C:13]([OH:15])=[O:14].O/[N:17]=[C:18](/[C:20]1[CH:34]=[CH:33][C:23]([CH2:24][N:25]2[CH2:28][CH:27]([C:29]([O:31][CH3:32])=[O:30])[CH2:26]2)=[CH:22][CH:21]=1)\[NH2:19].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(CC)CC>CN(C=O)C>[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:5]=[CH:4][C:3]=1[C:13]([O:15]/[N:17]=[C:18](/[C:20]1[CH:34]=[CH:33][C:23]([CH2:24][N:25]2[CH2:28][CH:27]([C:29]([O:31][CH3:32])=[O:30])[CH2:26]2)=[CH:22][CH:21]=1)\[NH2:19])=[O:14]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 7468145-Amino-1-phenyl-1H-pyrazole-4-carboxylic acidHCID 58504342HCID 58504342, compound

Product 1

HCID 58504345HCID 58504345, compoundYield 52.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 5-amino-1-phenyl-1H-pyrazole-4-carboxylic acid (90 mg, 0.441 mmol), (Z)-methyl 1-(4-(N′-hydroxycarbamimidoyl)benzyl)azetidine-3-carboxylate (116 mg, 0.441 mmol), EDC (84 mg, 0.441 mmol) and HOBT (67.5 mg, 0.441 mmol) in DMF (1 mL) was stirred at RT for 1 hr. At this time, Et3N (0.061 mL, 0.441 mmol) was added and stirring was continued at RT for 3 days. The mixture was then heated to 50° C. for 10 minutes. The reaction mixture was partitioned between EtOAc (30 mL) and saturated sodium bicarbonate solution (30 mL). The organic layer was washed with saturated sodium bicarbonate solution (30 mL), water (30 mL) and brine (30 mL). After drying (MgSO4) and filtration, the organic layer was concentrated to afford (Z)-methyl 1-(4-(N′-(5-amino-1-phenyl-1H-pyrazole-4-carbonyloxy)carbamimidoyl)benzyl)azetidine-3-carboxylate (103 mg, 0.230 mmol) as a white solid. HPLC retention time=1.05 minutes (PHENOMENEX® Luna 4.6×30 mm S-5 ODS column) eluting with 10-90% aqueous methanol+0.1% TFA over a 2 minute gradient. MS:(M+H)=449.3.

Workup

  1. stirringstirring
  2. waitwas continued at RT for 3 days
  3. temperatureThe mixture was then heated to 50° C. for 10 minutes
  4. customThe reaction mixture was partitioned between EtOAc (30 mL) and saturated sodium bicarbonate solution (30 mL)
  5. washThe organic layer was washed with saturated sodium bicarbonate solution (30 mL), water (30 mL) and brine (30 mL)
  6. customAfter drying
  7. filtration(MgSO4) and filtration
  8. concentrationthe organic layer was concentrated

Sources & evidence

ORD record
ord-340d26b303cb4f0bb5f8ecd054fc98c3
Source dataset
uspto-grants-2013_03
Patent number
US08389509B2

Reaction notes

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