Hydrochloric Acid → HCID 136009210, compound

HRID 1969539Notes

Reaction equation

HRID 1969539 reaction equation
[CH3:1][C@H:2]1[C@@H:6]([C:7]2[N:11]3[C:12]4[CH:18]=[CH:17][N:16](S(C5C=CC(C)=CC=5)(=O)=O)[C:13]=4[N:14]=[CH:15][C:10]3=[N:9][N:8]=2)[CH2:5][C@@H:4]([NH:29]C(=O)C)[CH2:3]1.[OH-].[Na+].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.C[C@H]1[C@@H](C2N3C4C=CN(S(C5C=CC(C)=CC=5)(=O)=O)C=4N=CC3=NN=2)C[C@@H](N)C1>[Pd].CO.CCOCC.O1CCOCC1>[CH3:1][C@H:2]1[C@@H:6]([C:7]2[N:11]3[C:12]4[CH:18]=[CH:17][NH:16][C:13]=4[N:14]=[CH:15][C:10]3=[N:9][N:8]=2)[CH2:5][C@@H:4]([NH2:29])[CH2:3]1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58557192HCID 58557192, compoundHCID 67998122HCID 67998122, compound

Product 1

HCID 136009210HCID 136009210, compoundYield 5%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 887MethanolSolvent3×HCID 3283Diethyl EtherSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of N-((1S,3R,4S)-3-methyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)acetamide (1.52 g, 3.36 mmol, prepared using Y from Example #7, step H and Pd/C, G, AA [Table 2, Method 3, Rt=6.1 min, or =ND], Z with NaOH, A with Example #1 Step D, HATU, and TEA, and B with TEA) and 1,4-dioxane (25 mL) was added aqueous HCl (6 N, 25 mL, 150 mmol). The reaction was heated at about 100° C. for about 14 h and then was cooled to ambient temperature and concd under reduced pressure. To the resulting brown residue was added MeOH (30 mL) and the solution was concd under reduced pressure. To the resulting residue was added MeOH (5 mL) followed by slow addition of Et2O (20 mL). Initially a cloudy solution formed and then a dark oil/gum formed and the mixture was concd under reduced pressure. To the resulting brown residue was added MeOH (30 mL), (1S,3R,4S)-3-methyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentan-amine (1.35 g, 2.50 mmol, UV purity 75%) from a separate reaction, and silica gel (7 g). The mixture was concd under reduced pressure and purified by silica gel chromatography eluting with a gradient of 0-100% (DCM/[2 M NH3 in MeOH] (9:1)) in DCM, the column was further flushed with MeOH then MeOH/aqueous NH4OH (9:1), to give (1S,3R,4S)-3-methyl-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanamine [Preparation #19.1] (0.092 g, 5%) as a dark brown solid: LC/MS (Table 1, Method a) Rt=1.35 min; MS m/z: 257 (M+H)+ and 2.9 g of brown residue that was partitioned between DCM and saturated aqueous NaHCO3 (50 mL each). The layers were separated and the aqueous layer was extracted with additional DCM (2×50 mL). The combined organic layers were washed with brine, dried over anhydrous MgSO4, filtered, and concd under reduced pressure to give (1S,3R,4S)-3-methyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanamine [Preparation #19.2](1.94 g, 78%) as a taupe foam: LC/MS (Table 1, Method a) Rt=1.80 min; MS m/z: 411 (M+H)+.

Workup

  1. customprepared
  2. temperaturewas cooled to ambient temperature
  3. customInitially a cloudy solution formed
  4. customa dark oil/gum formed
  5. customfrom a separate reaction, and silica gel (7 g)
  6. custompurified by silica gel chromatography
  7. washeluting with a gradient of 0-100% (DCM/[2 M NH3 in MeOH] (9:1)) in DCM
  8. customthe column was further flushed with MeOH

Sources & evidence

ORD record
ord-67f0ddc7f47e4d4b88d9c9f45de0f677
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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