Cyclopropanecarbonitrile → HCID 89857047, compound

HRID 931241Notes

Reaction equation

HRID 931241 reaction equation
Br[C:2]1[N:7]=[C:6]([C:8]2[NH:9][C:10]3[C:11]([N:29]=2)=[N:12][C:13]([N:16]2[CH2:21][CH2:20][CH2:19][C@@H:18]([C:22]([N:24]4[CH2:28][CH2:27][CH2:26][CH2:25]4)=[O:23])[CH2:17]2)=[CH:14][CH:15]=3)[CH:5]=[CH:4][CH:3]=1.[CH:30]1([C:33]#[N:34])[CH2:32][CH2:31]1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1(C)C=CC=CC=1.C1COCC1>[N:24]1([C:22]([C@@H:18]2[CH2:19][CH2:20][CH2:21][N:16]([C:13]3[N:12]=[C:11]4[N:29]=[C:8]([C:6]5[N:7]=[C:2]([C:30]6([C:33]#[N:34])[CH2:32][CH2:31]6)[CH:3]=[CH:4][CH:5]=5)[NH:9][C:10]4=[CH:15][CH:14]=3)[CH2:17]2)=[O:23])[CH2:28][CH2:27][CH2:26][CH2:25]1

Participants

6

Reactant 3

HCID 79637CyclopropanecarbonitrileHCID 2724254Sodium bis(trimethylsilyl)amideHCID 117966330HCID 117966330, compound

Product 1

HCID 89857047HCID 89857047, compoundYield 7%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of (R)-(1-(2-(6-bromopyridin-2-yl)-1H-imidazo[4,5-b]pyridin-5-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone (300 mg, 0.658 mmol) in toluene was added cyclopropane carbonitrile. The mixture was cooled to 0° C. then a 1M solution of sodium bis(trimethylsilyl)amide in THF was added dropwise. The reaction mixture was stirred for 16 h at room temperature. The mixture was quenched with water and then was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and was concentrated under reduced pressure. The residue was purified via preparative TLC (twice) to afford (R)-1-(6-(5-(3-(pyrrolidine-1-carbonyl)piperidin-1-yl)-1H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-yl)cyclopropanecarbonitrile (20 mg, 7%) MS (ES+APCI) (M+H) 442.2; LCMS retention time 2.969 min (Method C1); 1H NMR (400 MHz, CDCl3) δ 1.24-1.31 (m, 4H), 1.65-1.71 (m, 2H), 1.78-2.04 (m, 6H), 2.69 (m, 1H), 3.01 (t, 1H), 3.07-3.18 (m, 1H), 3.43-3.56 (m, 3H), 3.60-3.72 (m, 1H), 4.35 (br s, 1H), 4.54 (d, 1H), 6.72 (d, 1H), 7.48 (d, 1H), 7.79-7.95 (m, 2H), 8.58 (d, 1H), 10.28 (br s, 1H).

Workup

  1. customThe mixture was quenched with water
  2. extractionwas extracted with ethyl acetate
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. concentrationwas concentrated under reduced pressure
  5. customThe residue was purified via preparative TLC (twice)

Sources & evidence

ORD record
ord-d5d6ae510b2e463abb63fe2d2421dc52
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

Loading…