Cesium carbonate → HCID 68797591, compound

HRID 1893693Notes

Reaction equation

HRID 1893693 reaction equation
[Cl:1][C:2]1[C:3]([O:22][CH2:23][CH2:24][N:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]1[N:13]=[C:14]([NH:17][CH:18]([CH3:20])[CH3:19])[O:15][CH:16]=1)[CH:8]=[C:7]2[OH:21].C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:37][O:38][C:39]([C:41]1([NH:46][C:47]([CH:49]2[CH2:53][CH:52](OS(C3C=CC(Br)=CC=3)(=O)=O)[CH2:51][N:50]2[C:65](=O)[CH:66]([NH:71][C:72]([O:74][C:75]([CH3:78])([CH3:77])[CH3:76])=[O:73])[C:67]([CH3:70])([CH3:69])[CH3:68])=[O:48])[CH2:43][CH:42]1[CH:44]=[CH2:45])=[O:40].C(=O)(O)[O-].[Na+]>CN1C(=O)CCC1.CCOC(C)=O.[Cl-].[Li+].CO>[CH3:37][O:38][C:39]([C:41]1([NH:46][C:47]([CH:49]2[CH2:53][CH:52]([O:21][C:7]3[C:6]4[C:11](=[C:2]([Cl:1])[C:3]([O:22][CH2:23][CH2:24][N:25]5[CH2:26][CH2:27][O:28][CH2:29][CH2:30]5)=[CH:4][CH:5]=4)[N:10]=[C:9]([C:12]4[N:13]=[C:14]([NH:17][CH:18]([CH3:19])[CH3:20])[O:15][CH:16]=4)[CH:8]=3)[CH2:51][N:50]2[CH2:65][CH:66]([NH:71][C:72]([O:74][C:75]([CH3:78])([CH3:77])[CH3:76])=[O:73])[C:67]([CH3:69])([CH3:70])[CH3:68])=[O:48])[CH2:43][CH:42]1[CH:44]=[CH2:45])=[O:40]

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 76604909HCID 76604909, compound2×HCID 178456841HCID 178456841, compound

Product 1

HCID 68797591HCID 68797591, compoundYield 136.5%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolventHCID 433294Lithium ChlorideSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 8-chloro-2-(2-isopropylaminooxazol-4-yl)-7-(2-morpholin-4-yl-ethoxy)-quinolin-4-ol (341 mg, 0.63 mmol) and cesium carbonate (1.23 g, 3.78 mmol) in NMP was added 1-{[4-(4-bromobenzenesulfonyloxy)-1-(2-tert-butoxycarbonylamino-3,3-dimethylbutyryl)-pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid methyl ester (432 mg, 0.63 mmol) and the reaction was heated to 65° C. After 2 h an additional 0.5 eq of 1-{[4-(4-bromo-benzenesulfonyloxy)-1-(2-tert-butoxycarbonylamino-3,3-dimethyl-butyryl)-pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid methyl ester was added and stirred an additional hour. The reaction was diluted with EtOAc and 5% lithium chloride with stirring. The reaction was transferred to a separatory funnel and saturated sodium bicarbonate and MeOH (2 ml) was added. The layers were separated and the aqueous extracted again with EtOAc. The combined organic layers were then washed with 5% lithium chloride, dried over magnesium sulfated and concentrated to give 747 mg (99% yield) of 1-({1-(2-tert-butoxycarbonylamino-3,3-dimethylbutyl)-4-[8-chloro-2-(2-isopropylaminooxazol-4-yl)-7-(2-morpholin-4-yl-ethoxy)quinolin-4-yloxy]-pyrrolidine-2-carbonyl}-amino)-2-vinyl-cyclopropanecarboxylic acid methyl ester as a yellow oil. LCMS found 882.11 [M+H]+.

Workup

  1. stirringwith stirring
  2. customThe reaction was transferred to a separatory funnel
  3. customThe layers were separated
  4. extractionthe aqueous extracted again with EtOAc
  5. washThe combined organic layers were then washed with 5% lithium chloride
  6. dry with materialdried over magnesium
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-56bf2a229c924914baf407bd084b96cc
Source dataset
uspto-grants-2013_08
Patent number
US08513186B2

Reaction notes

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