2,3-dimethyl-1H-indol-5-amine → 2-Morpholin-4-yl-6-(2-morpholin-4-yl-ethoxy)-pyrimidine-4-carboxylic acid (2,3-dimethyl-1H-indol-5-yl)-amide

HRID 882744Notes

Reaction equation

HRID 882744 reaction equation
C[O:2][C:3]([C:5]1[CH:10]=[C:9]([O:11][CH2:12][CH2:13][N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[N:8]=[C:7]([N:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[N:6]=1)=O.[NH2:26][C:27]1[CH:28]=[C:29]2[C:33](=[CH:34][CH:35]=1)[NH:32][C:31]([CH3:36])=[C:30]2[CH3:37].C[Al](C)C>C1(C)C=CC=CC=1>[CH3:36][C:31]1[NH:32][C:33]2[C:29]([C:30]=1[CH3:37])=[CH:28][C:27]([NH:26][C:3]([C:5]1[CH:10]=[C:9]([O:11][CH2:12][CH2:13][N:14]3[CH2:15][CH2:16][O:17][CH2:18][CH2:19]3)[N:8]=[C:7]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)[N:6]=1)=[O:2])=[CH:35][CH:34]=2

Participants

5

Reactant 3

HCID 2586882,3-dimethyl-1H-indol-5-amineHCID 16682925TrimethylaluminumHCID 592586512-Morpholin-4-yl-6-(2-morpholin-4-yl-ethoxy)-pyrimidine-4-carboxylic acid methyl ester

Product 1

HCID 115766052-Morpholin-4-yl-6-(2-morpholin-4-yl-ethoxy)-pyrimidine-4-carboxylic acid (2,3-dimethyl-1H-indol-5-yl)-amide

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

To a stirred mixture of compound (I) (1.02 g, 2.9 mmol) and 5-amino-2,3-dimethylindole (488 mg, 3.04 mmol) in toluene (6.9 mL) that was heated briefly until components partly dissolved and cooled to ambient temperature, was added 2 M solution of trimethylaluminum in toluene (2.32 mL, 1.6 eq) drop-wise under nitrogen purge. Reaction mixture was stirred until bubbling (gas evolution) completed, and then heated at 115° C. (oil bath) for 15 minutes. To a cooled reaction mixture chloroform and 1 N NaOH were added, chloroform layer was separated, washed twice with water, brine and dried over anhydrous sodium sulfate. Flash column chromatography on silica gel (eluent dichloromethane-acetone-methanol (3:1:01)) and recrystallization from chloroform-ethyl acetate mixture afforded target amide, 2-Morpholin-4-yl-6-(2-morpholin-4-yl-ethoxy)-pyrimidine-4-carboxylic acid (2,3-dimethyl-1H-indol-5-yl)-amide, as a pale yellow solid (1.1 g, 79%).

Workup

  1. temperaturewas heated briefly until components
  2. dissolutionpartly dissolved
  3. custompurge
  4. customReaction mixture
  5. customuntil bubbling (gas evolution)
  6. temperatureheated at 115° C. (oil bath) for 15 minutes
  7. customTo a cooled reaction mixture chloroform and 1 N NaOH
  8. additionwere added
  9. customchloroform layer was separated
  10. washwashed twice with water, brine
  11. dry with materialdried over anhydrous sodium sulfate
  12. customFlash column chromatography on silica gel (eluent dichloromethane-acetone-methanol (3:1:01)) and recrystallization from chloroform-ethyl acetate mixture

Sources & evidence

ORD record
ord-e594fe13dabb459e8efe4a3919047b9e
Source dataset
uspto-grants-2012_08
Patent number
US08236795B2

Reaction notes

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