HCID 55296396, compound → 1H-Pyrrolo[3,2-b]pyridine-5-carbonitrile

HRID 1805294Notes

Reaction equation

HRID 1805294 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[C:35](=[N:36][C:37]([C:41]3([NH2:44])CC3)=[CH:38][CH:39]=2)[CH:34]=[CH:33]1>>[NH:32]1[C:40]2[C:35](=[N:36][C:37]([C:41]#[N:44])=[CH:38][CH:39]=2)[CH:34]=[CH:33]1

Participants

3

Reactant 2

HCID 55296396HCID 55296396, compoundHCID 592756803-(4-Fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methylbenzoic acid

Product 1

HCID 101032811H-Pyrrolo[3,2-b]pyridine-5-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-b]pyridin-5-yl)cyclopropanamine (obtained from 1H-pyrrolo[3,2-b]pyridine-5-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: 7.86-8.38 min. (UV detection at 220 nm). The material obtained was further purified by preparative TLC (500 um×20×20 cm plate, 5% MeOH/CH2Cl2). Analytical TLC Rf=0.30 (5% MeOH/CH2Cl2). 1H NMR (500 MHz, CD3OD) δ 7.96 (m, 2H), 7.90 (dd, J=7.93, 2.14, 1H), 7.83 (d, J=1.83, 1H), 7.72 (dd, J=8.55, 0.92, 1H), 7.54 (d, J=8.55, 1H), 7.51 (d, J=3.36, 1H), 7.48 (d, J=7.93, 1H), 7.34-7.27 (overlapping m, 4H), 6.55 (dd, J=3.36, 0.92, 1H), 2.96 (s, 3H), 2.29 (s, 3H), 1.69 (m, 2H), 1.38 (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)+=577.19, HPLC Rt=1.433 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=7.74 min; Column: Xbridge Phenyl 3.5 um, 4.6×150 mm, Rt=8.42 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=9.87 min. tert-butyl 1-(1,6-naphthyridin-2-yl)cyclopropylcarbamate was synthesized in a similar fashion then converted to 1-(1,6-naphthyridin-2-yl)cyclopropanamine using the following approach.

Sources & evidence

ORD record
ord-69123ef7cbab435fb92dbeaea38756db
Source dataset
uspto-grants-2013_01
Patent number
US08354410B2

Reaction notes

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