Water → 1-{2-Chloro-4-[6-[4-(3-diethylaminopropoxy)phenyl]-7-(2-trimethylsilanylethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy]phenyl}-3-cyclopropylurea

HRID 1433420Notes

Reaction equation

HRID 1433420 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:10]3[CH:17]=[C:16]([C:18]4[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH2:26][CH2:27][N:28]([CH2:31][CH3:32])[CH2:29][CH3:30])=[CH:20][CH:19]=4)[N:15]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:39])[CH3:38])[C:11]=3[N:12]=[CH:13][N:14]=2)[CH:5]=[CH:4][C:3]=1[NH2:41].[CH:42]1([NH:45][C:46](=O)[O:47]C2C=CC=CC=2)[CH2:44][CH2:43]1.O>CS(C)=O>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:10]3[CH:17]=[C:16]([C:18]4[CH:19]=[CH:20][C:21]([O:24][CH2:25][CH2:26][CH2:27][N:28]([CH2:29][CH3:30])[CH2:31][CH3:32])=[CH:22][CH:23]=4)[N:15]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:38])([CH3:39])[CH3:40])[C:11]=3[N:12]=[CH:13][N:14]=2)[CH:5]=[CH:4][C:3]=1[NH:41][C:46]([NH:45][CH:42]1[CH2:44][CH2:43]1)=[O:47]

Participants

5

Reactant 3

HCID 962WaterHCID 13648483Phenyl cyclopropylcarbamate2×HCID 589309462-Chloro-4-[6-[4-(3-diethylaminopropoxy)phenyl]-7-(2-trimethylsilanylethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy]phenylamine

Product 1

HCID 589310361-{2-Chloro-4-[6-[4-(3-diethylaminopropoxy)phenyl]-7-(2-trimethylsilanylethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy]phenyl}-3-cyclopropylurea

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

After dissolving the 2-chloro-4-[6-[4-(3-diethylaminopropoxy)phenyl]-7-(2-trimethylsilanylethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy]phenylamine synthesized in Production Example 160-2 in 0.6 ml of dimethylsulfoxide, 23 mg of phenyl cyclopropylcarbamate was added and the mixture was stirred at 80° C. for 1.5 hours. After further adding 75 mg of phenyl N-cyclopropylcarbamate and stirring at 100° C. for 5 hours, 70 mg of the same reagent was added prior to stirring overnight. The mixture was then returned to room temperature, water was added, and liquid separation and extraction were performed with an ethyl acetate: tetrahydrofuran (5:1) mixed solvent. The organic layer was dried over sodium sulfate, concentrated and subjected to NH silica gel column chromatography (hexane-ethyl acetate) to obtain 18 mg of the title compound.

Workup

  1. stirringstirring at 100° C. for 5 hours
  2. stirringto stirring overnight
  3. customwas then returned to room temperature
  4. customliquid separation and extraction
  5. additionmixed solvent
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-d281904981a54bc38c1d0e9e6da321a5
Source dataset
uspto-grants-2009_11
Patent number
US07612092B2

Reaction notes

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