Citric Acid → 1-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carboxylic acid (4-bromo-thiophen-2-ylmethyl)-amide

HRID 1625480Notes

Reaction equation

HRID 1625480 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH2:7][NH2:8])[S:5][CH:6]=1.[F:9][C:10]1[CH:11]=[C:12]([CH:24]=[CH:25][C:26]=1[F:27])[CH2:13][N:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20](O)=[O:21])[C:15]1=[O:23].F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.C(=O)(O)[O-]>[Cl-].[Na+].O.C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]([CH2:7][NH:8][C:20]([C:16]2[C:15](=[O:23])[N:14]([CH2:13][C:12]3[CH:24]=[CH:25][C:26]([F:27])=[C:10]([F:9])[CH:11]=3)[CH:19]=[CH:18][CH:17]=2)=[O:21])[S:5][CH:6]=1

Participants

9

Reactant 6

HCID 311Citric AcidHCID 769Bicarbonate IonHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 42282037(4-Bromothiophen-2-yl)methanamineHCID 534279691-(3,4-Difluorobenzyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid

Product 1

HCID 593627111-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carboxylic acid (4-bromo-thiophen-2-ylmethyl)-amide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

C-(4-Bromo-thiophen-2-yl)-methylamine (0.200 g, 0.00104 mol;), 1-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carboxylic acid (0.251 g, 0.000946 mol;), N,N,N′,N′-Tetramethyl-O-(7-azabenzotriazol-1-yl)uronium Hexafluorophosphate (0.40 g, 0.0010 mol;), N,N-Diisopropylethylamine (800 uL, 0.005 mol;), and Methylene chloride (9.1 mL, 0.14 mol;) were added to a 50 mL round bottom and stirred for 2 to 3 hours. LC-MS showed the formation of product at 1.78 438.92. Workup consisted of dilution with methylene chloride washing 1×with citric acid, 1× with saturated bicarbonate, and 1× with brine before drying and concentration to give the crude material. The crude was then purified by combiflash 0-100 percent hexanes/Ethyl acetate to give pure material. ES (+) MS m/e=438.92

Workup

  1. custombefore drying
  2. concentrationconcentration

Sources & evidence

ORD record
ord-1951dc89e932443a965c495934d6af89
Source dataset
uspto-grants-2014_07
Patent number
US08778977B2

Reaction notes

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