1,4-Dioxane hydrochloride → HCID 66551836, compound

HRID 922414Notes

Reaction equation

HRID 922414 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([CH:11]([N:13]([CH:29]2[CH2:31][CH2:30]2)[C:14]([C@@H:16]2[O:21][CH2:20][CH2:19][N:18](C(OC(C)(C)C)=O)[CH2:17]2)=[O:15])[CH3:12])[CH:8]=[C:7]2[C:3]=1[C:4]([CH3:37])=[N:5][N:6]2[CH2:32][CH2:33][CH2:34][O:35][CH3:36].Cl.O1CCOCC1>C(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:10]=[C:9]([C@H:11]([N:13]([CH:29]2[CH2:31][CH2:30]2)[C:14]([C@@H:16]2[O:21][CH2:20][CH2:19][NH:18][CH2:17]2)=[O:15])[CH3:12])[CH:8]=[C:7]2[C:3]=1[C:4]([CH3:37])=[N:5][N:6]2[CH2:32][CH2:33][CH2:34][O:35][CH3:36].[Cl:1][C:2]1[CH:10]=[C:9]([C@@H:11]([N:13]([CH:29]2[CH2:31][CH2:30]2)[C:14]([C@@H:16]2[O:21][CH2:20][CH2:19][NH:18][CH2:17]2)=[O:15])[CH3:12])[CH:8]=[C:7]2[C:3]=1[C:4]([CH3:37])=[N:5][N:6]2[CH2:32][CH2:33][CH2:34][O:35][CH3:36]

Participants

5

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 68309687HCID 68309687, compound

Product 2

HCID 66551836HCID 66551836, compoundHCID 68309688HCID 68309688, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of tert-butyl (2R)-2-{[{1-[4-chloro-1-(3-methoxypropyl)-3-methyl-1H-indazol-6-yl]ethyl}(cyclopropyl)amino]carbonyl}morpholine-4-carboxylate (146 mg) in chloroform (2.0 mL) was added 4-normal hydrogen chloride-dioxane solution (2.0 mL) under ice-cooling, and the mixture was stirred at room temperature for 3 hours. The reaction solution was concentrated under reduced pressure, and then thereto was added aqueous saturated sodium hydrogen carbonate solution under ice-cooling, and the mixture was extracted with chloroform. The organic layer was washed with saturated saline, dried over magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: chloroform/methanol/ammonia water=500/10/1) to give (2R)-N-{(1R)-1-[4-chloro-1-(3-methoxypropyl)-3-methyl-1H-indazol-6-yl]ethyl}-N-cyclopropylmorpholine-2-carboxamide [Ex(4-1)] (50.2 mg) and (2R)-N-{(1S)-1-[4-chloro-1-(3-methoxypropyl)-3-methyl-1H-indazol-6-yl]ethyl}-N-cyclopropylmorpholine-2-carboxamide [Ex(4-2)] (18.4 mg) as a colorless oil.

Workup

  1. temperaturecooling
  2. concentrationThe reaction solution was concentrated under reduced pressure
  3. additionwas added aqueous saturated sodium hydrogen carbonate solution under ice-
  4. temperaturecooling
  5. extractionthe mixture was extracted with chloroform
  6. washThe organic layer was washed with saturated saline
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue was purified by silica gel column chromatography (eluent: chloroform/methanol/ammonia water=500/10/1)

Sources & evidence

ORD record
ord-aadf20f906764313b4516c6eec525f42
Source dataset
uspto-grants-2016_03
Patent number
US09278944B2

Reaction notes

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