Pyrrolidine → HCID 178489412, compound

HRID 1865596Notes

Reaction equation

HRID 1865596 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[CH:19]=[N:20][CH:21]=[C:22]([CH:26]=3)[C:23](O)=[O:24])[CH:16]=2)[NH:11][N:10]=1.C1[CH:32]=[CH:31][C:30]([CH2:33][NH:34]S(C2C=CC3N=NN(O)C=3C=2)(=O)=O)=CC=1.Cl.CCN=C=NCCCN(C)C.Cl.N1CCCC1>CN(C=O)C.CN(C1C=CN=CC=1)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[CH:26]=[C:22]([C:23]([N:34]4[CH2:33][CH2:30][CH2:31][CH2:32]4)=[O:24])[CH:21]=[N:20][CH:19]=3)[CH:16]=2)[NH:11][N:10]=1

Participants

7

Reactant 4

HCID 31268PyrrolidineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 16217185HOBt resinHCID 178489413HCID 178489413, compound

Product 1

HCID 178489412HCID 178489412, compoundYield 6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

(5-[3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-nicotinic acid (350 mg, 62% pure, 0.63 mmol) was dissolved in anhydrous DMF (20 mL) at 50-60° C. and the solution was cooled to room temperature when PS-HOBt resin (Argonaut Technologies) (0.9 mmol·g−1 loading, 2.20 g, 1.98 mmol), DMAP (32 mg, 0.26 mmol) and EDCl (375 mg, 1.95 mmol) were added. The mixture was shaken at room temperature for 16 h. The resin was filtered off, washing six times with DMF and subsequently three times with ether and dried. The resin and (5-[3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-nicotinate) (460 mg, theoretical loading 105 μmol) were suspended in anhydrous DMF (3 mL) containing pyrrolidine (110 μl, 1.3 mmol) and shaken for 22 h. The resin is filtered off, washing with dichloromethane, ether and DMF. The filtrate and washings were combined and concentrated. The resulting residue is purified by mass-triggered reverse phase HPLC using a gradient of acetonitrile in water containing 0.1% of formic acid to afford {5-[3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-pyridin-3-yl}-pyrrolidin-1-yl-methanone (2.4 mg, 6 μmol, 6% yield) as a light brown solid. 1H-NMR (500 MHz, d6-MeOH) δ 8.98 (d, 1H), 8.87 (d, 1H), 8.74 (d, 1H), 8.50 (d, 1H), 8.31 (t, 1H), 7.67 (dd, 1H), 7.48 (ddd, 1H), 7.21 (d, 1H), 7.11 (dt, 1H), 3.89 (s, 3H), 3.65 (t, 2H), 3.58 (t, 2H), 2.02 (m, 2H), 1.96 (m, 2H). MS: m/z 400 [MH+].

Workup

  1. additionwere added
  2. filtrationThe resin was filtered off
  3. washwashing six times with DMF and subsequently three times with ether
  4. customdried
  5. stirringshaken for 22 h
  6. filtrationThe resin is filtered off
  7. washwashing with dichloromethane, ether and DMF
  8. concentrationconcentrated
  9. customThe resulting residue is purified by mass-triggered reverse phase HPLC

Sources & evidence

ORD record
ord-d679be9760a5488d82159d905910e530
Source dataset
uspto-grants-2009_12
Patent number
US07626021B2

Reaction notes

Loading…