Bromine → HCID 86605365, compound

HRID 2195075Notes

Reaction equation

HRID 2195075 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([Cl:39])[C:8]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[C:22]([C:24]4[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=4)[N:21]=[C:20]([N:31]4[CH2:36][CH2:35][O:34][CH2:33][C@H:32]4[CH3:37])[N:19]=3)[CH:14]([CH3:38])[CH2:13]2)=[N:9][C:10]=1N)=[O:4].[Br:40]Br.N([O-])=O.[Na+]>Br.C(O)(=O)C.O>[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([Cl:39])[C:8]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[C:22]([C:24]4[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=4)[N:21]=[C:20]([N:31]4[CH2:36][CH2:35][O:34][CH2:33][C@H:32]4[CH3:37])[N:19]=3)[CH:14]([CH3:38])[CH2:13]2)=[N:9][C:10]=1[Br:40])=[O:4]

Participants

7

Reactant 3

HCID 24408BromineHCID 23668193Sodium NitriteHCID 86605364HCID 86605364, compound

Product 1

HCID 86605365HCID 86605365, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolvent2×HCID 260Hydrogen BromideSolventHCID 962WaterSolvent

Conditions

Temperature
5 °C

Procedure

To a cooled (5° C.) and well stirred mixture of 6′-amino-3′-chloro-4-[6-(4-fluoro-phenyl)-2-(3-(R)-methyl-morpholin-4-yl)-pyrimidin-4-yl]-3-methyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-5′-carboxylic acid methyl ester (10 g) in 48% HBr (75 mL) and glacial acetic acid (120 mL), add a solution (16 mL) of bromine in acetic acid (6:1) over a period of 45 min. To this mixture add a solution of NaNO2 (8.3 g) in water (18 mL) while maintaining the temperature below 8° C. After the addition is complete, stir the mixture for 30 min and then destroy the excess bromine by adding 100 mL of 30% NaHSO3. Neutralize the solution to pH 8 by the dropwise addition of 20% NaOH and then extract with EtOAc. Wash the organic extracts with dilute NH4OH, dry (Na2SO4) and concentrate under reduced pressure to give the title compound.

Workup

  1. temperaturewhile maintaining the temperature below 8° C
  2. additionAfter the addition
  3. stirringstir the mixture for 30 min
  4. customdestroy the excess bromine
  5. additionby adding 100 mL of 30% NaHSO3
  6. additionby the dropwise addition of 20% NaOH
  7. extractionextract with EtOAc
  8. washWash the organic extracts with dilute NH4OH
  9. dry with materialdry (Na2SO4)
  10. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-d6b1b846b217426a8826e314f57ef996
Source dataset
uspto-grants-2012_12
Patent number
US08334382B2

Reaction notes

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