Potassium Carbonate → Potassium Carbonate

HRID 1407043Notes

Reaction equation

HRID 1407043 reaction equation
CCN([CH:7]([CH3:9])C)C(C)C.[Cl:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2([NH:20][C:21]3[N:26]=[C:25]([O:27][CH2:28][C:29]([F:32])([F:31])[F:30])[N:24]=[C:23]([NH:33][C:34]4[CH:56]=[CH:55][C:37]([C:38]([NH:40][C@@H:41](CNC(=O)C(OCC)=O)[C:42]([O:44][CH3:45])=[O:43])=[O:39])=[CH:36][CH:35]=4)[N:22]=3)[CH2:19][CH2:18]2)=[CH:13][CH:12]=1.CCN(C(C)C)C(C)C.CCN(C(N1N=N[N:80]([C:83]2[C:88](Cl)=CC=CC=2)[C:78]1=[O:79])=O)C1CCCCC1.[C:90](=[O:93])([O-:92])[O-:91].[K+:94].[K+]>CN1C(=O)CCC1.O.CN(C=O)C.CC(C)=O>[Cl:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2([NH:20][C:21]3[N:26]=[C:25]([O:27][CH2:28][C:29]([F:30])([F:32])[F:31])[N:24]=[C:23]([NH:33][C:34]4[CH:56]=[CH:55][C:37]([C:38]([NH:40][C@@H:41]([CH2:88][CH2:83][NH:80][C:78](=[O:79])[C:90]([O:92][CH2:7][CH3:9])=[O:91])[C:42]([O:44][CH3:45])=[O:43])=[O:39])=[CH:36][CH:35]=4)[N:22]=3)[CH2:19][CH2:18]2)=[CH:13][CH:12]=1.[C:90](=[O:91])([O-:93])[O-:92].[K+:94].[K+:94]

Participants

10

Reactant 4

HCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 3081363Fentrazamide2×HCID 131732199(S)-methyl 2-(4-((4-((1-(4-chlorophenyl)cyclopropyl)amino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-yl)amino)benzamido)-3-(2-ethoxy-2-oxoacetamido)propanoate DIPEA

Product 2

HCID 11430Potassium CarbonateHCID 89724286(S)-methyl 2-(4-((4-((1-(4-chlorophenyl)cyclopropyl)amino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-yl)amino)benzamido)-4-(2-ethoxy-2-oxoacetamido)butanoate

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A 0.08 M stock solution of the (S)-methyl 2-(4-((4-((1-(4-chlorophenyl)cyclopropyl)amino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-yl)amino)benzamido)-4-(2-ethoxy-2-oxoacetamido)butanoate in NMP was prepared and DIPEA (5.0 eq) was charged in. To each of the amines (15 eq) weighed into 16×100 mm threaded vials was added 1000 μLs of the (S)-methyl 2-(4-((4-((1-(4-chlorophenyl)cyclopropyl)amino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-yl)amino)benzamido)-3-(2-ethoxy-2-oxoacetamido)propanoate/DIPEA solution. The reactions were agitated at 350 rpm on an Innova platform shaker at room temperature for 48 hours. Samples were blown down using a Zymark tabletop dryer at 30° C. for 3 hours. A 1.8M solution of potassium carbonate in water was prepared. To each of the reaction vials was added 0.5 mL of acetone followed by 0.5 mls of the potassium carbonate solution. Vials were capped and agitated at 350 rpm on an Innova platform shaker at room temperature for 72 hours. Samples were blown down using a Zymark tabletop dryer at 30° C. for 3 hours before redissolving in 1 mL DMF each. Mixtures were transferred to a 96 well filter plate collecting into a 96 well deep-well plate. Reaction vials were rinsed with 500 μLs of DMF each and rinses were transferred to the appropriate wells of the filter plate. The desired products were isolated by preparative HPLC.

Workup

  1. customat 30° C.
  2. customfor 3 hours
  3. customTo each of the reaction vials
  4. customVials were capped
  5. customat 30° C.
  6. customfor 3 hours
  7. customcollecting into a 96 well deep-well plate
  8. customReaction vials
  9. washwere rinsed with 500 μLs of DMF each and rinses
  10. customThe desired products were isolated by preparative HPLC

Sources & evidence

ORD record
ord-3cf38f4a80864bedb14ce45adbf5c5bb
Source dataset
uspto-grants-2014_12
Patent number
US08916702B2

Reaction notes

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