N-(2-(p-bromophenoxy)ethyl)pyrrolidine → [5-(1-Benzyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-amine

HRID 1472855

Reaction equation

HRID 1472855 reaction equation
[CH2:1]([N:8]1[CH:12]=[C:11]([C:13]2[N:18]3[N:19]=[C:20]([NH2:22])[N:21]=[C:17]3[CH:16]=[CH:15][CH:14]=2)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:24]1[CH:37]=[CH:36][C:27]([O:28][CH2:29][CH2:30][N:31]2[CH2:35][CH2:34][CH2:33][CH2:32]2)=[CH:26][CH:25]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC(N(C)C)=O.O1CCOCC1>[CH2:1]([N:8]1[CH:12]=[C:11]([C:13]2[N:18]3[N:19]=[C:20]([NH:22][C:24]4[CH:25]=[CH:26][C:27]([O:28][CH2:29][CH2:30][N:31]5[CH2:32][CH2:33][CH2:34][CH2:35]5)=[CH:36][CH:37]=4)[N:21]=[C:17]3[CH:16]=[CH:15][CH:14]=2)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 70657N-(2-(p-bromophenoxy)ethyl)pyrrolidineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 445556945-(1-Benzyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine

Product 1

HCID 59590042[5-(1-Benzyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-amine

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
130 °C

Procedure

A microwave vial containing 5-(1-benzyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine (6.42 g, 22.1 mmol), 1-(2-(4-bromophenoxy)ethyl)pyrrolidine (5.1 mL, 24.3 mmol), tris(dibenzylideneacetone)dipalladium (0.633 g, 1.11 mmol), xantphos (1.28 g, 2.22 mmol), sodium tert-butoxide (4.34 g, 44.2 mmol) and 1,4-dioxane (50 mL) was heated under microwave irradiation (130° C., 15 min). Dimethylacetamide (2.5 mL) was added to assist with microwave absorption. The volatiles were removed under rotary evaporation, and the residue partitioned between ethyl acetate and water. The aqueous phase was extracted with ethyl acetate and the combined organics washed with water followed by brine. The organic phase was dried over magnesium sulfate, concentrated in vacuo and after trituration with the minimum amount of dichloromethane in diethylether afforded a pale yellow solid. Yield: 8.12 g, 77%; LCMS method: 2, RT: 2.52 min, MI: 480 [M+1].

Workup

  1. customto assist with microwave absorption
  2. customThe volatiles were removed under rotary evaporation
  3. customthe residue partitioned between ethyl acetate and water
  4. extractionThe aqueous phase was extracted with ethyl acetate
  5. washthe combined organics washed with water
  6. dry with materialThe organic phase was dried over magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customafter trituration with the minimum amount of dichloromethane in diethylether afforded a pale yellow solid

Sources & evidence

ORD record
ord-79c5bb45f2504259aa5eefdb4d843f3f
Source dataset
uspto-grants-2015_04
Patent number
US09012633B2

Linked notes

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