3-Cyanophenylboronic acid → 3-(3'-amino-2'-methyl-2'H-spiro[chroman-4,5'-[1,2,4]oxadiazole]-6-yl)benzonitrile

HRID 1408704Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:11]3([O:15][N:14]([CH3:16])[C:13]([NH2:17])=[N:12]3)[CH2:10][CH2:9][O:8][C:5]2=[CH:6][CH:7]=1.[C:18]([C:20]1[CH:21]=[C:22](B(O)O)[CH:23]=[CH:24][CH:25]=1)#[N:19]>O1CCOCC1.C([O-])([O-])=O.[Cs+].[Cs+].Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:17][C:13]1[N:14]([CH3:16])[O:15][C:11]2([C:4]3[C:5](=[CH:6][CH:7]=[C:2]([C:24]4[CH:25]=[C:20]([CH:21]=[CH:22][CH:23]=4)[C:18]#[N:19])[CH:3]=3)[O:8][CH2:9][CH2:10]2)[N:12]=1

Participants

Conditions

Temperature: 120 °C

Procedure

Pd(PPh3)2Cl2 (7 mg, 0.01 mmol) in a 10 mL flask under Ar was treated sequentially with 6-bromo-2′-methyl-2′H-spiro[chroman-4,5′-[1,2,4]oxadiazol]-3′-amine (59.4 mg, 0.2 mmol) in 1,4-dioxane (2.0 mL), Cs2CO3 (2 N, 1 mL) and 3-cyanophenylboronic acid (58.8 mg, 0.4 mmol). The mixture was heated at 120° C. under Ar in a microwave reactor for 30 minutes. The reaction mixture was concentrated in vacuo to give the residue, which was purified by preparative TLC and HPLC to give 3-(3′-amino-2′-methyl-2′H-spiro[chroman-4,5′-[1,2,4]oxadiazole]-6-yl)benzonitrile (6.7 mg, 10%). 1H-NMR (MeOD): 2.31 (m, 1H), 2.62 (m, 1H), 3.39 (m, 3H), 4.32 (m, 1H), 4.46 (m, 1H), 7.00 (d, 1H), 7.58-7.71 (m, 3H), 7.95 (m, 3H).

Workup

concentrationThe reaction mixture was concentrated in vacuo
customto give the residue, which
customwas purified by preparative TLC and HPLC

Sources & evidence

ORD record: ord-ac2ea34c2a8e41a1badc876a21e2545f
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08921359B2

Reaction notes

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