HCID 55296397, compound → 1H-Pyrrolo[3,2-c]pyridine-4-carbonitrile

HRID 1805293Notes

Reaction equation

HRID 1805293 reaction equation
FC1C2C(C(=O)NC)=C(C3C=CC(F)=CC=3)OC=2C=CC=1C1C=C(C=CC=1C)C(O)=O.[NH:32]1[C:40]2[CH:39]=[CH:38][N:37]=[C:36]([C:41]3([NH2:44])CC3)[C:35]=2[CH:34]=[CH:33]1>>[NH:32]1[C:40]2[CH:39]=[CH:38][N:37]=[C:36]([C:41]#[N:44])[C:35]=2[CH:34]=[CH:33]1

Participants

3

Reactant 2

HCID 55296397HCID 55296397, compoundHCID 592756803-(4-Fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methylbenzoic acid

Product 1

HCID 260764321H-Pyrrolo[3,2-c]pyridine-4-carbonitrile

Procedure

This example was prepared from the coupling of 3-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methylbenzoic acid with 1-(1H-pyrrolo[3,2-c]pyridin-4-yl)cyclopropanamine (obtained from 1H-pyrrolo[3,2-c]pyridine-4-carbonitrile by the reaction using Ti(OiPr)4/EtMgBr/BF3OEt2). Purification was performed by Shimadzu-VP preparative reverse phase HPLC using the separation method: Solvent A=10% MeOH-90% H2O-0.1% TFA, Solvent B=90% MeOH-10% H2O-0.1% TFA, Start % B=10, Final % B=100, Gradient time=10 min, Stop time=12 min, Flow Rate=25 mL/min, Column: Sunfire Prep C18 19×100 5 um, Fraction Collection: 7.86-8.40 min. (UV detection at 220 nm). The material obtained was further purified by preparative TLC (500 um×20×20 cm plate, 10% MeOH/CH2Cl2). Analytical TLC Rf=0.30 (10% MeOH/CH2Cl2). 1H NMR (500 MHz, CD3OD) δ 8.05 (d, J=5.80, 1H), 7.94 (m, 2H), 7.86 (d, J=7.93, 1H), 7.80 (s, 1H), 7.53 (d, J=8.55, 1H), 7.46 (d, J=8.24, 1H), 7.37 (d, J=3.36, 2H), 7.31-7.27 (overlapping m, 3H), 6.93 (d, J=3.05, 1H), 2.95 (s, 3H), 2.28 (s, 3H), 1.77 (m, 2H), 1.47 (m, 2H). LC/MS were performed by using Shimadzu-VP instrument with UV detection at 220 nm and Waters Micromass. HPLC method: Solvent A=10% MeOH-90% H2O-0.1% TFA, Solvent B=90% MeOH-10% H2O-0.1% TFA, Start % B=0, Final % B=100, Gradient time=2 min, Stop time=3 min, Flow Rate=5 ml/min, Column: Phenomenex-Luna, 3.0×50 mm, S10; (ES+) m/z (M+H)+=577.25, HPLC Rt=1.427 min. Analytical HPLC were performed by using Shimadzu-VP instrument with UV detection at 220 nm and 254 nm. Analytical HPLC method: Solvent A=5% MeCN-95% H2O-0.1% TFA, Solvent B=95% MeCN-5% H2O-0.1% TFA, Start % B=20, Final % B=100, Gradient time=15 min, Stop time=18 min, Flow Rate=1 ml/min, Column: Sunfire C18, 3.5 um, 4.6×150 mm, Rt=8.06 min; Column: Xbridge Phenyl 3.5 um, 4.6×150 mm, Rt=8.78 min. Analytical HPLC method: Solvent A=5% MeOH-95% H2O-10 mM NH4HCO3, Solvent B=95% MeOH-5% H2O-10 mM NH4HCO3, Start % B=50, Final % B=100, Gradient time=15 min, Stop time=18 min, Flow Rate=1 ml/min, Column: Xbridge Phenyl 3.5 um, 4.6×150 mm, Rt=10.20 min.

Sources & evidence

ORD record
ord-ec51f2137b7e409ca4d888293e0f4d78
Source dataset
uspto-grants-2013_01
Patent number
US08354410B2

Reaction notes

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