Dicyclohexylcarbodiimide → HCID 178479244, compound

HRID 624805Notes

Reaction equation

HRID 624805 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:32])=[C:6]([NH:8][C:9]2[CH:14]=[C:13]([NH:15][CH:16]3[CH2:18][CH2:17]3)[N:12]3[N:19]=[CH:20][C:21](/[CH:22]=[C:23]4/[C:24](=[O:31])[N:25]([CH2:29][OH:30])[C:26](=[O:28])[NH:27]/4)=[C:11]3[N:10]=2)[CH:7]=1.[NH:33](C(OC(C)(C)C)=O)[CH2:34][C:35](O)=[O:36].C1(N=C=NC2CCCCC2)CCCCC1>CN(C=O)C.CN(C1C=CN=CC=1)C.C(OCC)(=O)C>[ClH:1].[NH2:33][CH2:34][C:35]([O:30][CH2:29][N:25]1[C:24](=[O:31])/[C:23](=[CH:22]/[C:21]2[CH:20]=[N:19][N:12]3[C:13]([NH:15][CH:16]4[CH2:17][CH2:18]4)=[CH:14][C:9]([NH:8][C:6]4[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=4[F:32])=[N:10][C:11]=23)/[NH:27][C:26]1=[O:28])=[O:36]

Participants

7

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 78288N-(tert-butoxycarbonyl)glycineHCID 178517689HCID 178517689, compound

Product 1

HCID 178479244HCID 178479244, compoundYield 38.3%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To (Z)-5-((5-(5-chloro-2-fluorophenylamino)-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-3-yl)methylene)-3-(hydroxymethyl)imidazolidine-2,4-dione (100 mg, 0.218 mmol) in DMF (3 mL) was added Boc-Gly-OH (153 mg, 0.873 mmol), dicyclohexylcarbodiimide (180 mg, 0.873 mmol), and DMAP (13 mg, 0.109 mmol). The reaction mixture was stirred at room temperature overnight, then diluted with ethyl acetate and washed 1× with 1M HCl followed by 3× brine. The organic layer was dried with MgSO4, filtered and adsorbed onto silica gel. The crude material was purified by column chromatography eluting with 5-15% EtOAc/CH2Cl2 gradient. Pure fractions were combined and the solvent was removed. To the residue was added 4M HCl/dioxane (4 mL) and stirred at room temperature for 2 h. Removed excess HCl/dioxane. To the residue was added diethyl ether and the suspension was sonicated. The resulting solid was filtered off and washed with diethyl ether. Dried under vacuum to provide 23 mg (21%) of (Z)-(4-((5-(5-chloro-2-fluorophenylamino)-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-3-yl)methylene)-2,5-dioxoimidazolidin-1-yl)methyl 2-aminoacetate hydrogen chloride as a yellow solid. (LCMS (ES): >95% pure, m/z 515 [M+1]+.

Workup

  1. washwashed 1× with 1M HCl
  2. dry with materialThe organic layer was dried with MgSO4
  3. filtrationfiltered
  4. customThe crude material was purified by column chromatography
  5. washeluting with 5-15% EtOAc/CH2Cl2 gradient
  6. customthe solvent was removed
  7. additionTo the residue was added 4M HCl/dioxane (4 mL)
  8. stirringstirred at room temperature for 2 h
  9. additionTo the residue was added diethyl ether
  10. customthe suspension was sonicated
  11. filtrationThe resulting solid was filtered off
  12. washwashed with diethyl ether
  13. customDried under vacuum

Sources & evidence

ORD record
ord-93d5da40ae754c0a93bb28a15499696e
Source dataset
uspto-grants-2016_04
Patent number
US09303033B2

Reaction notes

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