Triethylamine → (1R,4R)-2-Oxa-5-azabicyclo[2.2.1]heptan-5-yl((R)-1-(2-(2-cyclopropylpyrimidin-4-yl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidin-3-yl)methanone

HRID 931266Notes

Reaction equation

HRID 931266 reaction equation
[CH:1]1([C:4]2[N:9]=[C:8]([C:10]3[NH:27][C:13]4=[N:14][C:15]([N:18]5[CH2:23][CH2:22][CH2:21][C@@H:20]([C:24](O)=[O:25])[CH2:19]5)=[CH:16][CH:17]=[C:12]4[N:11]=3)[CH:7]=[CH:6][N:5]=2)[CH2:3][CH2:2]1.C(N=C=NCCCN(C)C)C.[OH:39][C:40]1[C:48]2[N:47]=NN[C:44]=2[CH:43]=[CH:42]C=1.C(N(CC)CC)C.[C@@H]12O[C@@H](CC1)CNC2>CN(C)C=O.CN(C)C1C=CN=CC=1>[C@@H:43]12[CH2:44][C@@H:48]([N:47]([C:24]([C@@H:20]3[CH2:21][CH2:22][CH2:23][N:18]([C:15]4[N:14]=[C:13]5[NH:27][C:10]([C:8]6[CH:7]=[CH:6][N:5]=[C:4]([CH:1]7[CH2:3][CH2:2]7)[N:9]=6)=[N:11][C:12]5=[CH:17][CH:16]=4)[CH2:19]3)=[O:25])[CH2:42]1)[CH2:40][O:39]2

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 46831336(1R,5S)-8-oxa-3-azabicyclo[3.2.1]octaneHCID 178418300HCID 178418300, compoundHCID 178525786HCID 178525786, compound

Product 1

HCID 178521012(1R,4R)-2-Oxa-5-azabicyclo[2.2.1]heptan-5-yl((R)-1-(2-(2-cyclopropylpyrimidin-4-yl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidin-3-yl)methanoneYield 10.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of (R)-1-(2-(2-cyclopropylpyrimidin-4-yl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidine-3-carboxylic acid (70 mg, 0.192 mmol) in N,N-dimethylformamide (10 mL) were added 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDCl) (73.2 mg, 0.383 mmol), hydroxybenzotriazole (52 mg, 0.383 mmol), triethylamine (58.2 mg, 0.575 mmol), (1R,5S)-8-oxa-3-azabicyclo[3.2.1]octane (186 mg, 1.64 mmol) and 4-dimethylaminopyridine (3 mg) at room temperature. The reaction mixture was stirred for 18 h, poured into ice water, extracted with ethyl acetate, washed with cold water and concentrated. The crude was purified via preparative TLC (3% methanol in dichloromethane) to afford the title compound (9 mg). MS (ES+) (M+H) 446.3; LCMS retention time 1.816 min (Method F)

Workup

  1. extractionextracted with ethyl acetate
  2. washwashed with cold water
  3. concentrationconcentrated
  4. customThe crude was purified via preparative TLC (3% methanol in dichloromethane)

Sources & evidence

ORD record
ord-12165dc850eb4088ab70699b91a70412
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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