Oxygen → N-((1R,3R)-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)aniline

HRID 1969708Notes

Reaction equation

HRID 1969708 reaction equation
[C:1]1(B(O)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[S:10]([N:20]1[C:24]2[N:25]=[CH:26][C:27]3[N:28]([C:29]([C@@H:32]4[CH2:36][CH2:35][C@@H:34]([NH2:37])[CH2:33]4)=[N:30][N:31]=3)[C:23]=2[CH:22]=[CH:21]1)([C:13]1[CH:19]=[CH:18][C:16]([CH3:17])=[CH:15][CH:14]=1)(=[O:12])=[O:11].O=O>C(Cl)Cl.CC#N.O.C(O[Cu]OC(=O)C)(=O)C>[S:10]([N:20]1[C:24]2[N:25]=[CH:26][C:27]3[N:28]([C:29]([C@@H:32]4[CH2:36][CH2:35][C@@H:34]([NH:37][C:1]5[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=5)[CH2:33]4)=[N:30][N:31]=3)[C:23]=2[CH:22]=[CH:21]1)([C:13]1[CH:19]=[CH:18][C:16]([CH3:17])=[CH:15][CH:14]=1)(=[O:12])=[O:11]

Participants

7

Reactant 3

HCID 977Oxygen2×HCID 66827Phenylboronic AcidHCID 58557308(1R,3R)-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanamine

Product 1

HCID 67999555N-((1R,3R)-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)anilineYield 45%

Reagents, catalysts & solvents 3

HCID 178476682HCID 178476682, compoundCatalyst2×HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
40 °C

Procedure

A 100 mL round bottom flask was sequentially charged with phenylboronic acid (0.123 g, 1.01 mmol), diacetoxycopper monohydrate (0.010 g, 0.05 mmol), powdered 4 {acute over (Å)} molecular sieves (0.375 g) and DCM (4 mL). The reaction mixture was stirred for about 10 min then a suspension of (1R,3R)-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanamine (0.20 g, 0.50 mmol) in DCM (2 mL) and MeCN (2 mL) was added. The flask was fitted with an oxygen balloon. The flask was purged with oxygen and then heated at about 40° C. for about 18 h. Additional diacetoxycopper monohydrate (0.010 g, 0.05 mmol) was added and the reaction mixture was heated at about 45° C. under an atomosphere of oxygen for about 3 days. DCM (50 mL) was added and the reaction mixture was filtered through a pad of Celite® while washing with DCM (20 mL). The filtrate was concd under reduced pressure and the residue was purified using silica gel chromatography (20 g) eluting with a gradient of 30-80% EtOAc in DCM to give N-((1R,3R)-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)aniline (0.106 g, 45%): LC/MS (Table 1, Method b) Rt=2.39 min; MS m/z: 473 (M+H)+.

Workup

  1. additionwas added
  2. customThe flask was purged with oxygen
  3. filtrationthe reaction mixture was filtered through a pad of Celite®
  4. washwhile washing with DCM (20 mL)
  5. customthe residue was purified
  6. washeluting with a gradient of 30-80% EtOAc in DCM

Sources & evidence

ORD record
ord-364e2fc7b2234ee2a4775a1136d11cd3
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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