Oxalyl chloride → 5-Amino-N-[2-({[(2,6-dibromophenyl)carbonyl]amino}methyl)-3,3,3-trifluoro-2-hydroxypropyl]-1-(4-fluorophenyl)-1H-pyrazole-4-carboxamide

HRID 886727Notes

Reaction equation

HRID 886727 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([Br:11])[C:3]=1[C:4]([OH:6])=O.C(Cl)(=O)C(Cl)=O.[NH2:18][C:19]1[N:23]([C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)[N:22]=[CH:21][C:20]=1[C:31]([NH:33][CH2:34][C:35]([CH2:41][NH2:42])([OH:40])[C:36]([F:39])([F:38])[F:37])=[O:32].C(N(C(C)C)CC)(C)C>O1CCCC1.CN(C)C=O>[NH2:18][C:19]1[N:23]([C:24]2[CH:25]=[CH:26][C:27]([F:30])=[CH:28][CH:29]=2)[N:22]=[CH:21][C:20]=1[C:31]([NH:33][CH2:34][C:35]([CH2:41][NH:42][C:4]([C:3]1[C:7]([Br:11])=[CH:8][CH:9]=[CH:10][C:2]=1[Br:1])=[O:6])([OH:40])[C:36]([F:39])([F:38])[F:37])=[O:32]

Participants

7

Reactant 4

HCID 65578Oxalyl chloride2×HCID 81531DiisopropylethylamineHCID 44001432,6-Dibromobenzoic acidHCID 594874945-amino-N-[2-(aminomethyl)-3,3,3-trifluoro-2-hydroxypropyl]-1-(4-fluorophenyl)-1H-pyrazole-4-carboxamide

Product 1

HCID 594875125-Amino-N-[2-({[(2,6-dibromophenyl)carbonyl]amino}methyl)-3,3,3-trifluoro-2-hydroxypropyl]-1-(4-fluorophenyl)-1H-pyrazole-4-carboxamideYield 90.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of 2,6-dibromobenzoic acid (28 mg, 0.1 mmol) in anhydrous tetrahydrofuran (1 ml) was added anhydrous dimethylformamide (4 μl) followed by oxalyl chloride (100 μl of a 1 ml solution of 87 μl of oxalyl chloride in THF; 0.1 mmol). The mixture effervesced and was stirred under nitrogen for 45 minutes. A solution of 5-amino-N-[2-(aminomethyl)-3,3,3-trifluoro-2-hydroxypropyl]-1-(4-fluorophenyl)-1H-pyrazole-4-carboxamide (25.3 mg, 0.07 mmole) in anhydrous tetrahydrofuran (0.5 ml) and diisopropylethylamine (52 μl, 0.3 mmol) was added. It was then stirred under nitrogen at 21° C. for 3 days. It was blown down, partitioned between dichloromethane (5 ml) and 2M hydrochloric acid (2 ml). The organic layer was blown down and the residue purified on a 5 g SPE silica cartridge. Elution with dichloromethane then cyclohexane:ethyl acetate (10:1), (5:1), (3:1), (2:1) (3 times) and finally (1:1) (3 times). The title product was eluted in the third (2:1) fraction and the first (1:1) fraction. These fractions were combined and evaporated to give the title product (39.6 mg).

Workup

  1. stirringIt was then stirred under nitrogen at 21° C. for 3 days
  2. custompartitioned between dichloromethane (5 ml) and 2M hydrochloric acid (2 ml)
  3. customthe residue purified on a 5 g SPE silica cartridge
  4. washElution with dichloromethane
  5. washThe title product was eluted in the third (2:1) fraction
  6. customevaporated

Sources & evidence

ORD record
ord-3ef83d7dfc5f400393ade71905adde9f
Source dataset
uspto-grants-2012_08
Patent number
US08247377B2

Reaction notes

Loading…