2-Chloro-6-methylaniline → HCID 22125119, compound

HRID 1858261Notes

Reaction equation

HRID 1858261 reaction equation
[Si:1]([O:18][CH2:19][CH2:20][C:21]1[CH:22]=[C:23]([NH:27][C:28]2[C:33]([CH:34]=O)=[CH:32][N:31]=[C:30]([S:36][CH3:37])[N:29]=2)[CH:24]=[CH:25][CH:26]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:38][C:39]1[CH:45]=[CH:44][CH:43]=[C:42]([CH3:46])[C:40]=1[NH2:41].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1(C)C=CC=CC=1.O1CCCC1.O>[Si:1]([O:18][CH2:19][CH2:20][C:21]1[CH:22]=[C:23]([NH:27][C:28]2[C:33]([CH2:34][NH:41][C:40]3[C:42]([CH3:46])=[CH:43][CH:44]=[CH:45][C:39]=3[Cl:38])=[CH:32][N:31]=[C:30]([S:36][CH3:37])[N:29]=2)[CH:24]=[CH:25][CH:26]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 68972-Chloro-6-methylanilineHCID 521998p-Toluenesulfonic acid monohydrateHCID 21226445Aluminium lithium hydrideHCID 22125102HCID 22125102, compound

Product 1

HCID 22125119HCID 22125119, compoundYield 101%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2.6 g (5 mmol) of 4-(3-(2-(tert-butyldiphenylsilyloxy)ethyl)phenylamino)-5-formyl-2-methylthiopyrimidine and 0.63 ml (722 mg, 5.1 mmol) of 2-chloro-6-methylaniline in 80 ml of toluene was treated with 170 mg (0.9 mmol) of 4-toluenesulfonic acid monohydrate and then heated at reflux with azeotropic removal of water for 2 hours. The mixture was cooled and evaporated. The residue was dissolved in 20 ml of tetrahydrofuran and added dropwise to a solution of 5 ml (5 mmol) of lithium aluminium hydride (1M solution in tetrahydrofuran) in a further 30 ml of tetrahydrofuran. After stirring for 1 hour the reaction was quenched by the cautious dropwise addition of 1.5 ml of water, 2 ml of 2M aqueous sodium hydroxide and 2.5 ml of water. The mixture was filtered through a filter aid and the filtrate evaporated to give 3.3 g (100%) of 4-[3-(2-(tert-butyldiphenylsilyloxy)ethyl)phenyl]amino-5-(2-chloro-6-methylanilino)methyl-2-methylthiopyrimidine as a yellow oil which was used without further purification. [Mass spectrum (ESI) MH+ =653].

Workup

  1. temperatureheated
  2. temperatureThe mixture was cooled
  3. customevaporated
  4. dissolutionThe residue was dissolved in 20 ml of tetrahydrofuran
  5. customwas quenched by the cautious dropwise addition of 1.5 ml of water, 2 ml of 2M aqueous sodium hydroxide and 2.5 ml of water
  6. filtrationThe mixture was filtered through a filter aid
  7. customthe filtrate evaporated

Sources & evidence

ORD record
ord-c5b4bc430fd842a3a73619dda4ca0663
Source dataset
uspto-grants-2000_11
Patent number
US06150373

Reaction notes

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