5-cyanofuran-2-carboxylic Acid → 5-Cyano-furan-2-carboxylic acid[4-methyl-6'-(4-methyl-3-oxo-piperazin-1-yl)-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-3'-yl]-amide

HRID 646934Notes

Reaction equation

HRID 646934 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[N:13]=[C:12]([N:14]3[CH2:19][CH2:18][CH:17]([CH3:20])[CH2:16][CH2:15]3)[C:11]([N+:21]([O-])=O)=[CH:10][CH:9]=2)[CH2:4][C:3]1=[O:24].[C:25]([C:27]1[O:31][C:30]([C:32](Cl)=[O:33])=[CH:29][CH:28]=1)#[N:26].C(C1OC(C(O)=O)=CC=1)#N>C(Cl)Cl>[CH3:20][CH:17]1[CH2:18][CH2:19][N:14]([C:12]2[C:11]([NH:21][C:32]([C:30]3[O:31][C:27]([C:25]#[N:26])=[CH:28][CH:29]=3)=[O:33])=[CH:10][CH:9]=[C:8]([N:5]3[CH2:6][CH2:7][N:2]([CH3:1])[C:3](=[O:24])[CH2:4]3)[N:13]=2)[CH2:15][CH2:16]1

Participants

5

Reactant 3

HCID 108555165-cyanofuran-2-carboxylic AcidHCID 202590395-Cyano-2-furoyl chlorideHCID 586385151-Methyl-4-(4-methyl-3'-nitro-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-6'-yl)-piperazin-2-one

Product 1

HCID 114954975-Cyano-furan-2-carboxylic acid[4-methyl-6'-(4-methyl-3-oxo-piperazin-1-yl)-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-3'-yl]-amideYield 51%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-Methyl-4-(4-methyl-3′-nitro-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-6′-yl)-piperazin-2-one (as prepared in previous step) (166 mg, 0.50 mmol) was converted to the corresponding amine according to the procedure in Example 55, step (c) and coupled with 5-cyano-furan-2-carbonyl chloride as prepared in Example 4, step (c) (obtained from 137 mg, 1.00 mmol of 5-cyano-furan-2-carboxylic acid as prepared in Example 1) in CH2Cl2 (2 mL) at 0° C. The product was isolated by flash chromatography on silica (20% EtOAc/hexane-10% MeOH/EtOAc) to obtain the title compound (108 mg, 51%). 1H-NMR (CDCl3; 400 MHz): δ 8.73 (br s, 1H), 8.44 (d, 1H, J=8.7 Hz), 7.24 (d, 1H, J=3.7 Hz), 7.22 (d, 1H, J=3.7 Hz), 6.32 (d, 1H, J=8.7 Hz), 4.16 (m, 2H), 3.84 (m, 2H), 3.46 (m, 2H), 3.20 (m, 2H), 3.04 (s, 3H), 2.84 (m, 2H), 1.8 (m, 2H), 1.4 (m, 1H), 1.32 (m, 2H), 1.04 (d, 3H, J=6.3 Hz). LC-MS (ESI, m/z): Calcd. for C22H26N6O3, 423.2 (M+H), found 423.1

Workup

  1. customThe product was isolated by flash chromatography on silica (20% EtOAc/hexane-10% MeOH/EtOAc)

Sources & evidence

ORD record
ord-de2852eec22c4fd7baf18b7480d9a531
Source dataset
uspto-grants-2010_04
Patent number
US07705042B2

Reaction notes

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