Water → HCID 89442647, compound

HRID 632725Notes

Reaction equation

HRID 632725 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[CH:20]=[C:19]([Cl:21])[C:18]([Cl:22])=[CH:17][C:16]=3[OH:23])[CH2:10][CH2:9]2)[C:3]=1[C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=1.C(OC([N:38]1[CH2:41][CH:40](I)[CH2:39]1)=O)(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C>[NH:38]1[CH2:41][CH:40]([O:23][C:16]2[CH:17]=[C:18]([Cl:22])[C:19]([Cl:21])=[CH:20][C:15]=2[CH2:14][N:11]2[CH2:12][CH2:13][N:8]([C:4]3[N:5]=[CH:6][N:7]=[C:2]([NH2:1])[C:3]=3[C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=3)[CH2:9][CH2:10]2)[CH2:39]1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 11000522Tert-butyl 3-iodoazetidine-1-carboxylateHCID 89442445HCID 89442445, compound

Product 1

HCID 89442647HCID 89442647, compoundYield 40.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A reaction mixture of 2-{4-[6-amino-5-(4-fluoro-phenyl)-pyrimidin-4-yl]-piperazin-1-ylmethyl}-4,5-dichloro-phenol (80.0 mg; 0.18 mmol; 1.00 eq.), 3-iodo-azetidine-1-carboxylic acid tert-butyl ester (60.6 mg; 0.21 mmol; 1.20 eq.) and cesium carbonate (116.2 mg; 0.36 mmol; 2.00 eq.) in DMF (1 ml) was stirred at 90° C. overnight. The reaction solution was poured to water and extracted with ethyl acetate, The separated organic layer was washed with brine, dried and concentrated, which was then dissolved in methanol (1 ml) followed by adding 4.0 M HCl in dioxane (2 ml) and stirred at RT overnight. The reaction mixture was concentrated and purified by Waters prep-HPLC (acidic condition) to yield the title compounds (37 mg, yield 33.6%). LC-MS: (M+1=504, obsd.=504/506).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe separated organic layer was washed with brine
  3. customdried
  4. concentrationconcentrated
  5. dissolutionwhich was then dissolved in methanol (1 ml)
  6. additionby adding 4.0 M HCl in dioxane (2 ml)
  7. stirringstirred at RT overnight
  8. concentrationThe reaction mixture was concentrated
  9. custompurified by Waters prep-HPLC (acidic condition)

Sources & evidence

ORD record
ord-291fb5e366ba4ebab0cba7a5a334f975
Source dataset
uspto-grants-2016_04
Patent number
US09321760B2

Reaction notes

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