1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (6R)-9-fluoro-2,11,15,19,20,23-hexazapentacyclo[15.5.2.17,11.02,6.020,24]pentacosa-1(23),7,9,17(24),18,21-hexaene-16,25-dione

HRID 1426902Notes

Reaction equation

HRID 1426902 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][N:5]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]([C@H:12]2[CH2:16][CH2:15][CH2:14][N:13]2[C:17]2[CH:22]=[CH:21][N:20]3[N:23]=[CH:24][C:25]([C:26](O)=[O:27])=[C:19]3[N:18]=2)[C:6]1=[O:29].CN(C=O)C.C(Cl)Cl.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>CCOC(C)=O>[F:11][C:9]1[CH:8]=[C:7]2[C:6](=[O:29])[N:5]([CH:10]=1)[CH2:4][CH2:3][CH2:2][NH:1][C:26](=[O:27])[C:25]1=[C:19]3[N:18]=[C:17]([CH:22]=[CH:21][N:20]3[N:23]=[CH:24]1)[N:13]1[C@@H:12]2[CH2:16][CH2:15][CH2:14]1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 22350042dichloromethane N,N-dimethylformamideHCID 67471112(R)-5-(2-(1-(3-aminopropyl)-5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid

Product 1

HCID 54670253(6R)-9-fluoro-2,11,15,19,20,23-hexazapentacyclo[15.5.2.17,11.02,6.020,24]pentacosa-1(23),7,9,17(24),18,21-hexaene-16,25-dioneYield 39%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (R)-5-(2-(1-(3-aminopropyl)-5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (95 mg, 0.24 mmol) in 1:2 DMF/DCM (9 mL) was added EDCI (0.14 g, 0.71 mmol) followed by HOBT (96 mg, 0.71 mmol) at ambient temperature. After stirring for 10 minutes, TEA (0.099 mL, 0.71 mmol) was added to the reaction mixture and stirred for 6 hours. The reaction mixture was treated with EtOAc, washed with saturated NH4Cl, saturated NaHCO3, and brine, then dried (MgSO4), filtered, concentrated. The crude material was purified by silica column chromatography, eluting with 4% MeOH/DCM to yield the title product (35 mg, 39% yield). MS (apci) m/z=383.2 (M+H).

Workup

  1. stirringstirred for 6 hours
  2. washwashed with saturated NH4Cl, saturated NaHCO3, and brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified by silica column chromatography
  7. washeluting with 4% MeOH/DCM

Sources & evidence

ORD record
ord-e95cf7f44ced40f2b8e75913b596a5ca
Source dataset
uspto-grants-2015_01
Patent number
US08933084B2

Reaction notes

Loading…