P,P-Diphenylphosphinic azide → 4-(5-(1-Aminocyclopropyl)pyridin-3-yl)-2-chlorobenzonitrile

HRID 391328Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:11]=[C:12]([C:16]3(C(O)=O)[CH2:18][CH2:17]3)[CH:13]=[N:14][CH:15]=2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].C1(P([N:36]=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.CC([O-])(C)C.[K+]>C1(C)C=CC=CC=1.C1COCC1>[NH2:36][C:16]1([C:12]2[CH:11]=[C:10]([C:4]3[CH:5]=[CH:6][C:7]([C:8]#[N:9])=[C:2]([Cl:1])[CH:3]=3)[CH:15]=[N:14][CH:13]=2)[CH2:18][CH2:17]1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 1-(5-(3-chloro-4-cyanophenyl)pyridin-3-yl)cyclopropanecarboxylic acid (900 mg, 3.01 mmol) in toluene (50 mL) was added TEA (0.63 mL, 4.52 mmol) and diphenylphosphoryl azide (0.977 mL, 4.52 mmol), and the mixture was heated to 100° C. for 4 h. The mixture was then cooled to room temperature and concentrated in vacuo. The residue was re-dissolved in THF (100 mL) and a solution of KOtBu (2.03 g, 18.08 mmol) in THF (40 mL) was added. The mixture was stirred at 0° C. for 1 h. The mixture was then warmed to room temperature overnight. Silica gel (10 g) was added and the mixture was concentrated in vacuo. The residue was purified by silica chromatography eluting with a 0-10% MeOH-DCM gradient to give 4-(5-(1-aminocyclopropyl)pyridin-3-yl)-2-chlorobenzonitrile. m/z 270.0, 272.0 (M+H)+.

Workup

temperatureThe mixture was then cooled to room temperature
concentrationconcentrated in vacuo
dissolutionThe residue was re-dissolved in THF (100 mL)
temperatureThe mixture was then warmed to room temperature overnight
additionSilica gel (10 g) was added
concentrationthe mixture was concentrated in vacuo
customThe residue was purified by silica chromatography
washeluting with a 0-10% MeOH-DCM gradient

Sources & evidence

ORD record: ord-a69c51cb2fee4dffa9c7aac9d27013a5
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08383827B2

Reaction notes

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