1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (R)-(1-(2-(6-Cyclopropylpyridin-2-yl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidin-3-yl)(2,5-dihydro-1H-pyrrol-1-yl)methanone

HRID 931247Notes

Reaction equation

HRID 931247 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]([OH:26])=O)[CH2:19]5)=[CH:16][CH:17]=[C:12]4[N:11]=3)[CH:7]=[CH:6][CH:5]=2)[CH2:3][CH2:2]1.C(N=C=N[CH2:33][CH2:34][CH2:35][N:36]([CH3:38])C)C.OC1C2N=NNC=2C=CC=1.N1CC=CC1>CN(C)C=O>[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]([N:36]6[CH2:35][CH:34]=[CH:33][CH2:38]6)=[O:26])[CH2:19]5)=[CH:16][CH:17]=[C:12]4[N:11]=3)[CH:7]=[CH:6][CH:5]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 660593-PyrrolineHCID 178418300HCID 178418300, compoundHCID 178525785(R)-1-(2-(6-cyclopropylpyridin-2-yl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidine-3-carboxylic acid

Product 1

HCID 178521004(R)-(1-(2-(6-Cyclopropylpyridin-2-yl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidin-3-yl)(2,5-dihydro-1H-pyrrol-1-yl)methanoneYield 17%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of (R)-1-(2-(6-cyclopropylpyridin-2-yl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidine-3-carboxylic acid (150 mg, 0.686 mmol) in N,N-dimethylformamide (15 mL) was added 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (150 mg, 0.826 mmol), hydroxybenzotriazole (111 mg, 0.826 mmol), and 3-pyrroline (57 mg, 0.826 mmol) at room temperature. The reaction mixture was stirred for 24 h at room temperature then poured into ice water and extracted with ethyl acetate. The organic layer was concentrated under reduced pressure. The crude material was purified via preparative TLC (80% ethyl acetate in petroleum ether) to afford the title compound (30 mg, 17%). MS (ES+APCI) (M+H) 415.0; LCMS retention time 2.493 min (Method G). 1H NMR (300 MHz, CDCl3) δ 1.09 (m, 4H), 1.70 (m, 2H), 1.90 (m, 3H), 2.09 (m, 1H), 2.69 (m, 1H), 3.02 (m, 1H), 3.16 (m, 1H), 4.28 (m, 3H), 4.51 (m, 2H), 5.84 (m, 1H), 5.93 (m, 1H), 6.71 (d, 1H), 7.20 (d, 1H), 7.66 (m, 1H), 7.87 (d, 1H), 8.04 (m, 1H), 10.18 (br s, 1H).

Workup

  1. extractionextracted with ethyl acetate
  2. concentrationThe organic layer was concentrated under reduced pressure
  3. customThe crude material was purified via preparative TLC (80% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-7163473e3e364ffc9b3cedd830141238
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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