Dimethylformamide → tert-Butyl 5-[(cis-3,5-dimethylpiperazino)carbonyl]imidazo[1,5-a]quinoline-3-carboxylate

HRID 1585156Notes

Reaction equation

HRID 1585156 reaction equation
[CH3:1][C:2]([CH3:5])([O-:4])[CH3:3].[K+].[CH3:7][C@H:8]1[NH:13][C@@H:12]([CH3:14])[CH2:11][N:10]([C:15]2[C:16](Cl)=[N:17][C:18]3[C:23]([C:24]=2[C:25](N)=O)=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH2:9]1.C[C:30]([C:33]1ON=C(C[N+]#[C-])[N:34]=1)(C)C.CN([CH:44]=[O:45])C.C1C[O:49]CC1>O>[CH3:14][C@H:12]1[NH:13][C@@H:8]([CH3:7])[CH2:9][N:10]([C:15]([C:24]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[N:17]3[CH:16]=[N:34][C:33]([C:44]([O:4][C:2]([CH3:5])([CH3:3])[CH3:1])=[O:45])=[C:30]3[CH:25]=2)=[O:49])[CH2:11]1

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 8028TetrahydrofuranHCID 107257105-(1,1-Dimethylethyl)-3-isocyanomethyl-1,2,4-oxadiazoleHCID 23665647Potassium tert-butoxideHCID 86750212cis-3,5-Dimethylpiperazino 2-chloroquinoline-4-carboxamide

Product 1

HCID 22869039tert-Butyl 5-[(cis-3,5-dimethylpiperazino)carbonyl]imidazo[1,5-a]quinoline-3-carboxylate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Potassium tert-butoxide (2.6 ml, 1.0 M in THF) is added to a mixture of cis-3,5-dimethylpiperazino 2-chloroquinoline-4-carboxamide (X, 704 mg), tert-butyl isocyanoacetate (IX, 390 mg) and DMF (10 ml) at -78°. The mixture is stirred for 1 hr at -78° and is allowed to warm to 20-25° over several hours. After stirring at 20-25° for 16 hrs, water is added and the mixture extracted several times with ethyl acetate, the combined organic phases are dried over magnesium sulfate, filtered, and concentrated to provide a mixture of product and starting material, which is resubmitted to the above conditions (THF used instead of DMF). Purification of the resultant crude material by flash chromatography (silica gel; ethyl acetate/methanol (4/1)) provides the product. Recrystallization from hot ethyl acetate/hexane gives the desired title compound, mp 233-234°; IR (mineral oil) 1719, 1615, 1607, 1388, 1270, 1128 cm-1 ; NMR (CDCl3) 8.67, 7.95-8.15, 7.65-7.9, 7.54, 4.7-4.85, 3.35-3.55, 2.4-3.1, 1.68, 1.22 and 0.85-1.05 δ; MS (EI, m/e) 408, 351, 335, 307, 239, 195 and 113.

Workup

  1. temperatureto warm to 20-25° over several hours
  2. stirringAfter stirring at 20-25° for 16 hrs
  3. extractionthe mixture extracted several times with ethyl acetate
  4. dry with materialthe combined organic phases are dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto provide
  8. additiona mixture of product
  9. customPurification of the resultant crude material by flash chromatography (silica gel; ethyl acetate/methanol (4/1))
  10. customprovides the product
  11. customRecrystallization from hot ethyl acetate/hexane

Sources & evidence

ORD record
ord-986b41a154374c1c8fcfeca96803f3ac
Source dataset
uspto-grants-1999_08
Patent number
US05935970

Reaction notes

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