Potassio isocyanate → (S)-1-(3-(4-Amino-6-((1-(5-methyl-4-oxo-3-phenyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl)amino)pyrimidin-5-yl)-5-methoxyphenyl)urea

HRID 1052843Notes

Reaction equation

HRID 1052843 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C@H:9]([C:11]2[N:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:15](=[O:23])[C:14]3=[C:24]([CH3:27])[CH:25]=[CH:26][N:13]3[N:12]=2)[CH3:10])[C:3]=1[C:28]1[CH:33]=[C:32]([O:34][CH3:35])[CH:31]=[C:30]([NH2:36])[CH:29]=1.[N-:37]=[C:38]=[O:39].[K+]>O.C(O)(=O)C.C(OCC)(=O)C>[NH2:1][C:2]1[C:3]([C:28]2[CH:29]=[C:30]([NH:36][C:38]([NH2:37])=[O:39])[CH:31]=[C:32]([O:34][CH3:35])[CH:33]=2)=[C:4]([NH:8][C@H:9]([C:11]2[N:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:15](=[O:23])[C:14]3=[C:24]([CH3:27])[CH:25]=[CH:26][N:13]3[N:12]=2)[CH3:10])[N:5]=[CH:6][N:7]=1

Participants

6

Reactant 2

HCID 11051572Potassio isocyanateHCID 118433902(S)-2-(1-((6-Amino-5-(3-amino-5-methoxyphenyl)pyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one

Product 1

HCID 90102996(S)-1-(3-(4-Amino-6-((1-(5-methyl-4-oxo-3-phenyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl)amino)pyrimidin-5-yl)-5-methoxyphenyl)ureaYield 57.1%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

(S)-2-(1-((6-Amino-5-(3-amino-5-methoxyphenyl)pyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (87 mg, 0.18 mmol) was suspended in a mixture of water (1.5 ml) and acetic acid (1.5 ml) and cooled in an ice bath to 0° C. This mixture was treated with a solution of potassium isocyanate (29 mg, 0.36 mmol) in water (0.5 ml). The reaction mixture was stirred at 0° C. for 1 h and then led to warm to room temperature. The crude was diluted with ethyl acetate and washed with saturated ammonium chloride solution and brine. After evaporation of the solvent, the residue was purified by flash chromatography (50 to 100%, hexane-ethyl acetate) using SP1® Purification System to give 54 mg (57% yield) of the title compound as a solid. Purity 99%.

Workup

  1. temperatureto warm to room temperature
  2. washwashed with saturated ammonium chloride solution and brine
  3. customAfter evaporation of the solvent
  4. customthe residue was purified by flash chromatography (50 to 100%, hexane-ethyl acetate)
  5. customSP1® Purification System

Sources & evidence

ORD record
ord-42be8d9b461842939f9a4dffd1d30d8f
Source dataset
uspto-grants-2016_07
Patent number
US09388189B2

Reaction notes

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