N-Hydroxyacetamidine → N-ethanimidoyl-3-[2-methoxy-6-[2-(4-methoxyphenyl)ethylamino]pyrimidin-4-yl]benzamide

HRID 2110672Notes

Reaction equation

HRID 2110672 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[C:7]([C:9]2[CH:10]=[C:11]([CH:15]=[CH:16][CH:17]=2)[C:12]([OH:14])=O)[CH:6]=[C:5]([NH:18][CH2:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=2)[N:4]=1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[C:60](=[N:63]O)([NH2:62])[CH3:61]>CN(C)C=O.O>[NH:62]=[C:60]([NH:63][C:12](=[O:14])[C:11]1[CH:15]=[CH:16][CH:17]=[C:9]([C:7]2[CH:6]=[C:5]([NH:18][CH2:19][CH2:20][C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=3)[N:4]=[C:3]([O:2][CH3:1])[N:8]=2)[CH:10]=1)[CH3:61]

Participants

7

Reactant 4

HCID 30926N-HydroxyacetamidineHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 116033013-{2-Methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-benzoic acid

Product 1

HCID 148920926N-ethanimidoyl-3-[2-methoxy-6-[2-(4-methoxyphenyl)ethylamino]pyrimidin-4-yl]benzamideYield 69%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-{2-methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-benzoic acid (200 mg, 0.53 mmol, Example 35(a)] in dimethylformamide (1.75 mL) is added diisopropylethylamine (0.23 mL, 1.33 mmol) followed by TBTU (205 mg, 0.64 mmol). Stirred the solution for 15 minutes before adding acetamide oxime (59 mg, 0.8 mmol). After 4 hours of stirring at ambient temperature the mixture is diluted with water (20 mL) and extracted twice with EtOAc (20 mL). The combined organic extracts are washed three times with water (20 mL), with brine (20 mL), dried over magnesium sulfate, filtered and concentrated by rotary evaporator to provide N-(1-imino-ethyl)-3-{2-methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-benzamide [60 mg, 69%, Intermediate (45)].

Workup

  1. stirringAfter 4 hours of stirring at ambient temperature the mixture
  2. extractionextracted twice with EtOAc (20 mL)
  3. washThe combined organic extracts are washed three times with water (20 mL)
  4. dry with materialwith brine (20 mL), dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated by rotary evaporator

Sources & evidence

ORD record
ord-7efe5feef7bf4640ac96953155820124
Source dataset
uspto-grants-2009_04
Patent number
US07517889B2

Reaction notes

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