Bicarbonate Ion → Morpholin-4-yl-{3-[2-(2,2,6,6-tetramethyl-piperidin-4-ylamino)-pyrimidin-4-yl]-1H-indol-6-yl}-methanone

HRID 1435047Notes

Reaction equation

HRID 1435047 reaction equation
[CH3:1][C:2]1([CH3:37])[CH2:7][CH:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]3[C:23]4[C:18](=[CH:19][C:20]([C:24](O)=[O:25])=[CH:21][CH:22]=4)[N:17](COCC[Si](C)(C)C)[CH:16]=3)[CH:12]=[CH:11][N:10]=2)[CH2:5][C:4]([CH3:36])([CH3:35])[NH:3]1.S(Cl)(Cl)=O.[NH:42]1[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1.C(=O)(O)[O-].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>ClC(Cl)C.CN(C1C=CN=CC=1)C.CCOC(C)=O.CN(C=O)C>[N:42]1([C:24]([C:20]2[CH:19]=[C:18]3[C:23]([C:15]([C:13]4[CH:12]=[CH:11][N:10]=[C:9]([NH:8][CH:6]5[CH2:5][C:4]([CH3:36])([CH3:35])[NH:3][C:2]([CH3:37])([CH3:1])[CH2:7]5)[N:14]=4)=[CH:16][NH:17]3)=[CH:22][CH:21]=2)=[O:25])[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1

Participants

10

Reactant 5

HCID 769Bicarbonate IonHCID 8083MorpholineHCID 24386Thionyl ChlorideHCID 2724141Tetrabutylammonium FluorideHCID 579361353-[2-(2,2,6,6-Tetramethyl-piperidin-4-ylamino)-pyrimidin-4-yl]-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indole-6-carboxylic acid

Product 1

HCID 57936152Morpholin-4-yl-{3-[2-(2,2,6,6-tetramethyl-piperidin-4-ylamino)-pyrimidin-4-yl]-1H-indol-6-yl}-methanone

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 63651,1-DichloroethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A suspension of 3-[2-(2,2,6,6-Tetramethyl-piperidin-4-ylamino)-pyrimidin-4-yl]-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indole-6-carboxylic acid (542 mg, 1.0 mmol) in dichloroethane was treated with 3 equivalents of thionyl chloride. A drop of DMF was added and the clear solution was stirred at room temperature for 10 min. This solution was added to a solution of morpholine (1.30 g, 14.9 mmol) in dichloroethane containing DMAP (5.00 mg). After 2 h the reaction mixture was given into a saturated bicarbonate solution, extracted with DCM and dried over sodium sulfate. After removal of the solvent the yellow residue was dissolved in THF and treated with 10 equivalents of TBAF under reflux for 8 h. The reaction mixture was given into EtOAc, washed with 2.5M NaOH, dried over sodium sulfate and concentrated. Purification via chromatography on silicagel (EtOAc/MeOH/ammonia:95/4/1 to 80/19/1) gave the title compound as a white solid. Yield: 250 mg (54%).

Workup

  1. extractionextracted with DCM
  2. dry with materialdried over sodium sulfate
  3. customAfter removal of the solvent the yellow residue
  4. dissolutionwas dissolved in THF
  5. temperatureunder reflux for 8 h
  6. washwashed with 2.5M NaOH
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customPurification via chromatography on silicagel (EtOAc/MeOH/ammonia:95/4/1 to 80/19/1)

Sources & evidence

ORD record
ord-619f8f8a70574a43bece5ca92cb8d2c3
Source dataset
uspto-grants-2009_11
Patent number
US07615562B2

Reaction notes

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