Methyl iodide → HCID 60112881, compound

HRID 445176Notes

Reaction equation

HRID 445176 reaction equation
[CH:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH2:21][C:22]#[CH:23])[CH:18]=3)[N:13]([CH2:24][C:25]3[CH:26]=[C:27]([NH:31][C:32](=[O:44])[CH2:33][N:34]4[CH2:39][CH2:38][N:37]([CH2:40][CH2:41][O:42][CH3:43])[CH2:36][CH2:35]4)[CH:28]=[CH:29][CH:30]=3)[C:12](=[O:45])[N:11]=2)=[CH:6][CH:5]=1)([CH3:3])[CH3:2].[Li+].[CH3:47]C([N-]C(C)C)C.CN(P(N(C)C)(N(C)C)=O)C.CI>>[CH:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH2:21][C:22]#[CH:23])[CH:18]=3)[N:13]([CH2:24][C:25]3[CH:26]=[C:27]([N:31]([CH3:47])[C:32](=[O:44])[CH2:33][N:34]4[CH2:39][CH2:38][N:37]([CH2:40][CH2:41][O:42][CH3:43])[CH2:36][CH2:35]4)[CH:28]=[CH:29][CH:30]=3)[C:12](=[O:45])[N:11]=2)=[CH:6][CH:5]=1)([CH3:3])[CH3:2]

Participants

5

Reactant 4

HCID 6328Methyl iodideHCID 12679HexamethylphosphoramideHCID 2724682Lithium diisopropylamideHCID 10210971HCID 10210971, compound

Product 1

HCID 60112881HCID 60112881, compound

Conditions

Temperature
-78 °C

Procedure

A solution of 1.20 g (2 mmol) of N-{3-[4-(4-isopropyl-phenyl)-2-oxo-6-propargyloxy-2H-quinazolin-1-ylmethyl]-phenyl}-2-[4-(2-methoxy-ethyl)-piperazin-1-yl]-acetamide is treated with 4.1 ml 0.5 M LDA-solution (in THF) and 0.35 ml (2.0 mmol) HMPT at −78° C. The cooling bath is removed and stirring continued for half an hour while the solution turns slowly red. The reaction mixture is cooled down again to −78° C., 284 μl methyl iodide (2 mmol; diluted with 5 ml THF) is added. After stirring overnight at rt, the orange solution is concentrated in vacuo The yellow foamy residue is purified by chromatography (CH2Cl2/MeOH 9:1). Yield: 480 mg (13%) yellow foam.

Workup

  1. customThe cooling bath is removed
  2. waitcontinued for half an hour while the solution
  3. stirringAfter stirring overnight at rt
  4. concentrationthe orange solution is concentrated in vacuo The yellow foamy residue
  5. customis purified by chromatography (CH2Cl2/MeOH 9:1)

Sources & evidence

ORD record
ord-14a3eecf07994c378ba0e72d5ea97594
Source dataset
uspto-grants-2013_07
Patent number
US08476286B2

Reaction notes

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