1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 178489412, compound

HRID 272026Notes

Reaction equation

HRID 272026 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.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 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 31268PyrrolidineHCID 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 EDCI (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) δ8.98 (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-1582d4fe595c4d03b7636cade74306ab
Source dataset
uspto-grants-2008_11
Patent number
US07452993B2

Reaction notes

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