Hydrochloric Acid → (1R,3S)-2,2-dimethyl-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclobutanamine

HRID 2204518Notes

Reaction equation

HRID 2204518 reaction equation
[CH3:1][C:2]1([CH3:32])[C@@H:5]([C:6]2[N:10]3[C:11]4[CH:17]=[CH:16][N:15]([S:18]([C:21]5[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=5)(=[O:20])=[O:19])[C:12]=4[N:13]=[CH:14][C:9]3=[N:8][N:7]=2)[CH2:4][C@H:3]1[NH:28]C(=O)C.C(N[C@@H]1C[C@H](C(O)=O)C1(C)C)(=O)C.CCN(C(C)C)C(C)C.Cl>O1CCOCC1.C(Cl)CCl>[CH3:1][C:2]1([CH3:32])[C@@H:5]([C:6]2[N:10]3[C:11]4[CH:17]=[CH:16][N:15]([S:18]([C:21]5[CH:22]=[CH:23][C:24]([CH3:25])=[CH:26][CH:27]=5)(=[O:20])=[O:19])[C:12]=4[N:13]=[CH:14][C:9]3=[N:8][N:7]=2)[CH2:4][C@H:3]1[NH2:28]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 11183048(1S,3R)-3-acetamido-2,2-dimethylcyclobutane-1-carboxylic acidHCID 58010256N-((1R,3S)-2,2-dimethyl-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclobutyl)acetamide

Product 1

HCID 58010300(1R,3S)-2,2-dimethyl-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclobutanamineYield 78%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of N-((1R,3S)-2,2-dimethyl-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclobutyl)acetamide (2.20 g, 4.86 mmol, prepared using A from Preparation #9 and (1S,3R)-3-acetamido-2,2-dimethylcyclobutanecarboxylic acid [prepared as described in Tetrahedron: Asymmetry 2008, 19, 302-308] with EDC, C with DIEA) in 1,4-dioxane (30 mL) was added 6 N aqueous HCl (32.4 mL, 194 mmol). The reaction was heated at about 100° C. for about 16 h. The reaction was allowed to cool to ambient temperature and was partitioned between EtOAc (500 mL) and aqueous NaHCO3 (500 mL). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give (1R,3S)-2,2-dimethyl-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclobutanamine (1.56 g, 78%) as a tan solid: LC/MS (Table 2, Method a) Rt=1.60 min; MS m/z: 411 (M+H)+.

Workup

  1. temperatureto cool to ambient temperature
  2. customwas partitioned between EtOAc (500 mL) and aqueous NaHCO3 (500 mL)
  3. dry with materialThe organic layer was dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-652a69a8ae584d8594d6ba0718b8d422
Source dataset
uspto-grants-2016_06
Patent number
US09365579B2

Reaction notes

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