Methyl iodide → HCID 54071097, compound

HRID 1858113Notes

Reaction equation

HRID 1858113 reaction equation
CN(C)P([N:8]([CH3:10])[CH3:9])(N(C)C)=O.[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][CH2:22][CH2:21][C@H:20]1[CH2:25][CH2:26][O:27][C:28]1[C:37]2C(=[CH:33][C:34]([Cl:48])=[C:35]([NH:38][C:39]([NH:41][C:42]3[CH:47]=[CH:46][N:45]=[CH:44][N:43]=3)=[O:40])[CH:36]=2)N[C:30](=[O:49])[C:29]=1[C:50]1[CH:55]=[C:54]([CH3:56])[CH:53]=[C:52]([CH3:57])[CH:51]=1)=[O:18])([CH3:15])([CH3:14])[CH3:13].I[CH3:59]>O1CCCC1>[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][CH2:22][CH2:21][C@H:20]1[CH2:25][CH2:26][O:27][C:28]1[C:37]2[C:10](=[CH:33][C:34]([Cl:48])=[C:35]([N:38]([CH3:59])[C:39]([NH:41][C:42]3[CH:47]=[CH:46][N:45]=[CH:44][N:43]=3)=[O:40])[CH:36]=2)[N:8]([CH3:9])[C:30](=[O:49])[C:29]=1[C:50]1[CH:51]=[C:52]([CH3:57])[CH:53]=[C:54]([CH3:56])[CH:55]=1)=[O:18])([CH3:14])([CH3:15])[CH3:13]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 12679HexamethylphosphoramideHCID 54003851HCID 54003851, compound

Product 1

HCID 54071097HCID 54071097, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of lithium bis(trimethylamide) (0.43 mL of a 1M solution in 1.0 mL dry tetrahydrofuran) at -78° C. was added 0.198 mL hexamethylphosphoramide (HMPA) followed by a solution of (S)-2-{2-[7-chloro-3-(3,5-dimethylphenyl)-2-oxo-6-(3-pyrimidin-4-yl-ureido)-1,2-dihydroquinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid tert-butyl ester (prepared essentially as described in EXAMPLE 1, 69 mg in 1.5 mL dry tetrahydrofuran) and the mixture stirred at low temperature for 75 minutes. At this time, 0.036 mL of iodomethane was added and the mixture warmed to 0° C. After 4 hours, the reaction was quenched by the addition of IN hydrochloric acid, extracted with methylene chloride washed with brine and dried over magnesium sulfate. Purification of the concentrate by flash chromatography on silica gel (ethyl acetate:hexane 3:7; then 5:5; then 7:3) gave the title compound (30 mg).

Workup

  1. customprepared essentially
  2. waitAfter 4 hours
  3. customthe reaction was quenched by the addition of IN hydrochloric acid
  4. extractionextracted with methylene chloride
  5. washwashed with brine
  6. dry with materialdried over magnesium sulfate
  7. customPurification of the
  8. concentrationconcentrate by flash chromatography on silica gel (ethyl acetate:hexane 3:7

Sources & evidence

ORD record
ord-bd28e2f3f57445ae93f3359d3057392a
Source dataset
uspto-grants-2000_11
Patent number
US06150352

Reaction notes

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