1,1'-Carbonyldiimidazole → HCID 59570823, compound

HRID 1685022Notes

Reaction equation

HRID 1685022 reaction equation
Cl.[Cl:2][CH2:3][C:4]1[N:5]=[C:6]([NH2:9])[S:7][CH:8]=1.C1N=CN([C:15]([N:17]2C=N[CH:19]=[CH:18]2)=[O:16])C=1.CCN(C(C)C)C(C)C.[F:31][C:32]1[CH:33]=C([CH:37]=[C:38]([F:40])[CH:39]=1)CN>>[Cl:2][CH2:3][C:4]1[N:5]=[C:6]([NH:9][C:15]([NH:17][CH2:18][C:19]2[CH:33]=[C:32]([F:31])[CH:39]=[C:38]([F:40])[CH:37]=2)=[O:16])[S:7][CH:8]=1

Participants

5

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 732282-Thiazolamine, 4-(chloromethyl)-, hydrochloride (1:1)2×HCID 81531Diisopropylethylamine2×HCID 1452113,5-Difluorobenzylamine

Product 1

HCID 59570823HCID 59570823, compound

Procedure

A 3-neck 500 ml round bottle flask was charged with 4-Chloromethyl-thiazol-2-ylamine hydrochloride (Intermediate 1, 1 eq.) and CDI (1.05 eq.) and purged with nitrogen. Anhydrous THF was added via cannula. To the resulting stirring granular suspension was added DIPEA (1.05 eq.) dropwise via an addition funnel. After the addition of DIPEA was complete, the 3,5-difluoro-benzyl amine (1.0 eq.) was added dropwise in the same manner. The reaction was quenched with DI water and the THF was removed in vacuo. The resulting orange residue was partitioned with water and DCM. The organic layer was dried with Na2SO4, filtered and solvent was removed in vacuo. The crude was purified by column chromatography (acetone/hexanes) followed by recrystallization from iPrOAc and hexanes. The solid was isolated via filtration and dried under vacuum to give 1-(4-Chloromethyl-thiazol-2-yl)-3-(3,5-difluoro-benzyl)-urea.

Workup

  1. custompurged with nitrogen
  2. additionAnhydrous THF was added via cannula
  3. customThe reaction was quenched with DI water
  4. customthe THF was removed in vacuo
  5. customThe resulting orange residue was partitioned with water and DCM
  6. dry with materialThe organic layer was dried with Na2SO4
  7. filtrationfiltered
  8. customsolvent was removed in vacuo
  9. customThe crude was purified by column chromatography (acetone/hexanes)
  10. customfollowed by recrystallization from iPrOAc and hexanes
  11. customThe solid was isolated via filtration
  12. customdried under vacuum

Sources & evidence

ORD record
ord-0a1b3407e51c43f1886d68d7add0ed11
Source dataset
uspto-grants-2012_04
Patent number
US08148380B2

Reaction notes

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