Chloride → N,N-Diethyl-2-{3-methyl-4-[3-methyl-2-oxo-8-(2-pyrrolidin-1-yl-pyrimidin-5-yl)-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl]-pyrazol-1-yl}-acetamide

HRID 445782Notes

Reaction equation

HRID 445782 reaction equation
[CH3:1][C:2]1[C:6]([N:7]2[C:19]3[C:18]4[CH:17]=[C:16]([C:20]5[CH:21]=[N:22][C:23]([N:26]6[CH2:30][CH2:29][CH2:28][CH2:27]6)=[N:24][CH:25]=5)[CH:15]=[CH:14][C:13]=4[N:12]=[CH:11][C:10]=3[N:9]([CH3:31])[C:8]2=[O:32])=[CH:5][N:4]([CH2:33][C:34](O)=[O:35])[N:3]=1.CN(C=O)C.[Cl-].[CH2:43]([NH:45][CH2:46][CH3:47])[CH3:44]>ClCCl.C([O-])(O)=O.[Na+]>[CH2:43]([N:45]([CH2:46][CH3:47])[C:34](=[O:35])[CH2:33][N:4]1[CH:5]=[C:6]([N:7]2[C:19]3[C:18]4[CH:17]=[C:16]([C:20]5[CH:21]=[N:22][C:23]([N:26]6[CH2:30][CH2:29][CH2:28][CH2:27]6)=[N:24][CH:25]=5)[CH:15]=[CH:14][C:13]=4[N:12]=[CH:11][C:10]=3[N:9]([CH3:31])[C:8]2=[O:32])[C:2]([CH3:1])=[N:3]1)[CH3:44]

Participants

7

Reactant 4

HCID 312ChlorideHCID 6228DimethylformamideHCID 8021DiethylamineHCID 59620034{3-Methyl-4-[3-methyl-2-oxo-8-(2-pyrrolidin-1-yl-pyrimidin-5-yl)-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl]-pyrazol-1-yl}-acetic acid

Product 1

HCID 49835031N,N-Diethyl-2-{3-methyl-4-[3-methyl-2-oxo-8-(2-pyrrolidin-1-yl-pyrimidin-5-yl)-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl]-pyrazol-1-yl}-acetamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of {3-methyl-4-[3-methyl-2-oxo-8-(2-pyrrolidin-1-yl-pyrimidin-5-yl)-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl]-pyrazol-1-yl}-acetic acid (Stage 247.1.1, 0.12 mmol) and DMF (0.007 ml) in dichloromethane (2 ml) was added oxallyl chloride (0.36 mmol) and the RM was stirred for 45 min at rt. The RM was quenched with diethylamine (Riedel-deHaën, Buchs, Switzerland, 2.4 mmol) and stirred for 5 min at it then diluted with saturated aqueous NaHCO3 and extracted with EtOAc (2×). The combined organic layers were washed with brine (2×), dried over Na2SO4, filtered and evaporated. The residue was taken in MeOH/DMF and purified by preparative HPLC. The fractions containing pure product were basified with NaHCO3, concentrated, cooled at 4° C. and the precipitate was filtered, washed with water and dried under vacuum to give the title compound as white solid. (HPLC: tR 2.63 min (Method A); M+H=540 MS-ES; 1H-NMR (d6-DMSO, 400 MHz) 8.92 (s, 1H), 8.57 (s, 2H), 8.07-8.04 (m, 2H), 7.87-7.84 (m, 1H), 7.67-7.65 (m, 1H), 5.21-5.04 (m, 2H), 3.57 (s, 3H), 3.52-3.46 (m, 4H), 3.42-3.34 (m, 2H), 3.32-3.34 (m, 2H), 1.96-1.90 (m, 4H), 1.94 (s, 3H), 1.18 (t, 3H), 0.99 (t, 3H))

Workup

  1. stirringstirred for 5 min at it
  2. extractionextracted with EtOAc (2×)
  3. washThe combined organic layers were washed with brine (2×)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. custompurified by preparative HPLC
  8. additionThe fractions containing pure product
  9. concentrationconcentrated
  10. temperaturecooled at 4° C.
  11. filtrationthe precipitate was filtered
  12. washwashed with water
  13. customdried under vacuum

Sources & evidence

ORD record
ord-eccc8141ad4c4a80be525c5ec6fc37e3
Source dataset
uspto-grants-2013_07
Patent number
US08476294B2

Reaction notes

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