N,N,N',N'-Tetramethylethylenediamine → (S)-tert-butyl 3-((6-cyano-1,7-naphthyridin-8-yl)oxy)pyrrolidine-1-carboxylate

HRID 1476856Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([O:12][C@H:13]3[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14]3)[N:11]=1)[N:8]=[CH:7][CH:6]=[CH:5]2.[CH3:25][N:26](C)CCN(C)C.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>CS(C)=O.CCOC(C)=O.[C-]#N.[Zn+2].[C-]#N.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:25]([C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([O:12][C@H:13]3[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14]3)[N:11]=1)[N:8]=[CH:7][CH:6]=[CH:5]2)#[N:26]

Participants

Conditions

Temperature: 160 °C

Procedure

A solution of (S)-tert-butyl 3-((6-bromo-1,7-naphthyridin-8-yl)oxy)pyrrolidine-1-carboxylate (1400 mg, 3.55 mmol), zinc cyanide (834 mg, 7.1 mmol) and N1,N1,N2,N2-tetramethylethane-1,2-diamine (0.106 mL, 0.71 mmol) in DMSO (9 mL) was degassed with nitrogen for 5 minutes. Xantphos (206 mg, 0.355 mmol) and Pd2(dba)3 (325 mg, 0.355 mmol) were added and the mixture was heated in a microwave reactor at 160° C. for 15 minutes. The reaction mixture was diluted with EtOAc and washed with water (2×). The organic layer was separated and concentrated in vacuo. The crude product was purified by silica column chromatography to give the title compound as a yellow solid (181 mg, 15%).

Workup

washwashed with water (2×)
customThe organic layer was separated
concentrationconcentrated in vacuo
customThe crude product was purified by silica column chromatography

Sources & evidence

ORD record: ord-4f7a2ec0d6a14d2a8799e71f8e867209
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09402841B2

Reaction notes

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