Theobromine → N-(5-chloropyridin-2-yl)-2-[((4-((2,3,4,5,6,7-hexahydro-3,7-dimethyl-2,6-dioxo-1H-purin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide

HRID 370113Notes

Reaction equation

HRID 370113 reaction equation
[NH:1]1[C:12](=[O:13])[C:11]2[N:9]([CH3:10])[CH:8]=[N:7][C:6]=2[N:4]([CH3:5])[C:2]1=[O:3].C(N(CC)O)C.[Cl:20][C:21]1[CH:22]=[CH:23][C:24]([NH:27][C:28](=[O:49])[C:29]2[CH:34]=[C:33]([Cl:35])[CH:32]=[C:31]([O:36][CH3:37])[C:30]=2[NH:38][C:39]([C:41]2[S:42][CH:43]=[C:44]([CH2:47]Cl)[C:45]=2[Cl:46])=[O:40])=[N:25][CH:26]=1.C([O-])([O-])=O.[K+].[K+]>O.CN(C=O)C>[Cl:20][C:21]1[CH:22]=[CH:23][C:24]([NH:27][C:28](=[O:49])[C:29]2[CH:34]=[C:33]([Cl:35])[CH:32]=[C:31]([O:36][CH3:37])[C:30]=2[NH:38][C:39]([C:41]2[S:42][CH:43]=[C:44]([CH2:47][N:1]3[C:12](=[O:13])[CH:11]4[CH:6]([N:7]=[CH:8][N:9]4[CH3:10])[N:4]([CH3:5])[C:2]3=[O:3])[C:45]=2[Cl:46])=[O:40])=[N:25][CH:26]=1

Participants

7

Reactant 4

HCID 5429TheobromineHCID 11430Potassium CarbonateHCID 19463DiethylhydroxylamineHCID 16731661N-(5-chloropyridin-2-yl)-2-[((4-(chloromethyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide

Product 1

HCID 18376574N-(5-chloropyridin-2-yl)-2-[((4-((2,3,4,5,6,7-hexahydro-3,7-dimethyl-2,6-dioxo-1H-purin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

In a similar manner to that described in Paragraph F above, to a solution of theobromine (1.06 g, 5.9 mmol), N,N-diethylhydroxylamine (0.45 g, 5.0 mmol), N-(5-chloropyridin-2-yl)-2-[((4-(chloromethyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide (0.32 g, 0.6 mmol), and DMF (40 mL) was added K2CO3 (0.74 g, 5.3 mmol). The mixture was stirred at 40° C. for 6 days, then it was poured into water. The solid was isolated by filtration. Purification by recrystallization from CH2Cl2 and CH3OH afforded N-(5-chloropyridin-2-yl)-2-[((4-((2,3,4,5,6,7-hexahydro-3,7-dimethyl-2,6-dioxo-1H-purin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide, as a white solid; NMR (DMSO-d6) 10.90 (s, 1H), 9.40 (s, 1H), 8.36 (d, 1H), 8.12 (d, 1H), 8.06 (s, 1H), 7.90 (dd, 1H), 7.55 (s, 1H), 7.38 (d, 1H), 7.27 (d, 1H), 4.97 (s, 2H), 3.90 (s, 6H), 3.40 (s, 3H) ppm.

Workup

  1. customThe solid was isolated by filtration
  2. customPurification
  3. customby recrystallization from CH2Cl2 and CH3OH

Sources & evidence

ORD record
ord-272722d082fe46e2b770357f5e4e4960
Source dataset
uspto-grants-2000_10
Patent number
US06140351

Reaction notes

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