1-BOC-6-AMINO-INDAZOLE → HCID 136041739, compound

HRID 880078Notes

Reaction equation

HRID 880078 reaction equation
[N:1]1([C:7]2[N:8]=[C:9]([CH2:14][C:15]([O-:17])=O)[NH:10][C:11](=[O:13])[CH:12]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[Na+].C([N:26]1[C:34]2[C:29](=[CH:30][CH:31]=[C:32]([NH2:35])[CH:33]=2)[CH:28]=[N:27]1)(OC(C)(C)C)=O>>[NH:26]1[C:34]2[C:29](=[CH:30][CH:31]=[C:32]([NH:35][C:15](=[O:17])[CH2:14][C:9]3[NH:10][C:11](=[O:13])[CH:12]=[C:7]([N:1]4[CH2:2][CH2:3][O:4][CH2:5][CH2:6]4)[N:8]=3)[CH:33]=2)[CH:28]=[N:27]1

Participants

3

Reactant 2

HCID 120186071-BOC-6-AMINO-INDAZOLEHCID 136041844Sodium (4-morpholin-4-yl-6-oxo-1,6-dihydropyrimidin-2-yl)acetate

Product 1

HCID 136041739HCID 136041739, compoundYield 5.6%

Conditions

Temperature
100 °C

Procedure

The product is prepared according to the procedure described in Example 19, using 261 mg of sodium [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate prepared in stage 2 of Example 1 and 280 mg of 1-Boc-6-aminoindazole in place of the 3-(tert-butyl)aniline. The reaction mixture is concentrated under reduced pressure and taken up in 13 ml of 1,4-dioxane and 3 ml of 1N hydrochloric acid, and is then microwave-heated for 10 minutes at 100° C. After cooling to ambient temperature, the reaction mixture is concentrated under reduced pressure and taken up in 30 ml of water, and then a saturated aqueous solution of sodium bicarbonate is added so as to obtain a pH in the region of 8. The precipitate formed is filtered off and washed with water, ethyl acetate and ethyl ether. After purification by silica column chromatography, elution being carried out with a gradient of the eluent CH2Cl2/MeOH: 7030 in dichloromethane of 0% to 100%, 20 mg of N-(1H-indazol-6-yl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide are obtained in the form of a white solid, the characteristics of which are the following:

Workup

  1. customThe product is prepared
  2. concentrationThe reaction mixture is concentrated under reduced pressure
  3. temperatureAfter cooling to ambient temperature
  4. concentrationthe reaction mixture is concentrated under reduced pressure
  5. additiona saturated aqueous solution of sodium bicarbonate is added so as
  6. customto obtain a pH in the region of 8
  7. customThe precipitate formed
  8. filtrationis filtered off
  9. washwashed with water, ethyl acetate and ethyl ether
  10. customAfter purification
  11. washby silica column chromatography, elution

Sources & evidence

ORD record
ord-09441923f2b642098cecee85a0b9c4d1
Source dataset
uspto-grants-2015_03
Patent number
US08993565B2

Reaction notes

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