Dimethylformamide → N-(2-Amino-1-cyano-2-oxoethyl)-5-chloro-6-[4-(2-oxo-2H-3,1-benzoxazin-1(4H)-yl)piperidin-1-yl]pyridine-3-carboxamide

HRID 2414339Notes

Reaction equation

HRID 2414339 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:25](O)=[O:26])[CH:5]=[N:6][C:7]=1[N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=3[CH2:17][O:16][C:15]2=[O:24])[CH2:10][CH2:9]1.C(Cl)(=O)C(Cl)=O.C[N:35](C)[CH:36]=[O:37].C([N:42](CC)[CH:43]([CH3:45])C)(C)C.C[N:49]1CCCC1=O>ClCCl>[NH2:35][C:36](=[O:37])[CH:45]([NH:49][C:25]([C:4]1[CH:5]=[N:6][C:7]([N:8]2[CH2:13][CH2:12][CH:11]([N:14]3[C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=4[CH2:17][O:16][C:15]3=[O:24])[CH2:10][CH2:9]2)=[C:2]([Cl:1])[CH:3]=1)=[O:26])[C:43]#[N:42]

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 13387N-methyl-2-pyrrolidoneHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 226445845-Chloro-6-[4-(2-oxo-2h-3,1-benzoxazin-1(4h)-yl)piperidin-1-yl]pyridine-3-carboxylic acid

Product 1

HCID 22644626N-(2-Amino-1-cyano-2-oxoethyl)-5-chloro-6-[4-(2-oxo-2H-3,1-benzoxazin-1(4H)-yl)piperidin-1-yl]pyridine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The product of example 148 step (i) (0.14 g) was stirred as a suspension in dichloromethane (4 ml) and to this mixture was added oxalyl chloride (0.05 g) followed by N,N-dimethylformamide (0.01 g). After stirring for 1 h at room temperature the mixture was treated with 2-aminocyanoacetanide (0.14 g) 1-methyl-2-pyrrolidinone (3 ml) and then N,N-diisopropylethylamine (1 ml), stirring was then continued for a further 18 h at room temperature. The reaction mixture was partitioned between aqueous sodium bicarbonate and ethyl acetate, the organic layer was washed with water, dried and evaporated under reduced pressure. Purification was by chromatography eluting with 25% ethyl acetate/isohexane. Yield 0.09 g as a solid.

Workup

  1. waitwas then continued for a further 18 h at room temperature
  2. customThe reaction mixture was partitioned between aqueous sodium bicarbonate and ethyl acetate
  3. washthe organic layer was washed with water
  4. customdried
  5. customevaporated under reduced pressure
  6. customPurification
  7. washeluting with 25% ethyl acetate/isohexane

Sources & evidence

ORD record
ord-e81565842d6f45cb973086b00fe0a1d1
Source dataset
uspto-grants-2004_11
Patent number
US06812226B2

Reaction notes

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