Cesium carbonate → 6-(3,5-difluorophenyl)-2'-methyl-2-(tetrahydro-2H-pyran-3-yl)-2'H-spiro[chroman-4,5'-[1,2,4]oxadiazol]-3'-amine

HRID 1408697Notes

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][CH:9]([CH:18]3[CH2:23][CH2:22][CH2:21][O:20][CH2:19]3)[O:8][C:5]2=[CH:6][CH:7]=1.[F:24][C:25]1[CH:26]=[C:27](B(O)O)[CH:28]=[C:29]([F:31])[CH:30]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.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>[F:24][C:25]1[CH:26]=[C:27]([C:2]2[CH:3]=[C:4]3[C:11]4([O:15][N:14]([CH3:16])[C:13]([NH2:17])=[N:12]4)[CH2:10][CH:9]([CH:18]4[CH2:23][CH2:22][CH2:21][O:20][CH2:19]4)[O:8][C:5]3=[CH:6][CH:7]=2)[CH:28]=[C:29]([F:31])[CH:30]=1

Participants

Conditions

Temperature: 120 °C

Procedure

In a 10 mL flask, 6-bromo-2′-methyl-2-(tetrahydro-2H-pyran-3-yl)-2′H-spiro[chroman-4,5′-[1,2,4]oxadiazol]-3′-amine (30 mg, 0.08 mmol), Pd(PPh3)2Cl2 (15 mg), 3,5-difluorophenylboronic acid (25 mg, 0.16 mg) were dissolved in 1,4-dioxane (4.0 mL), followed by addition of Cs2CO3 (2 N, 1 mL). 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 6-(3,5-difluorophenyl)-2′-methyl-2-(tetrahydro-2H-pyran-3-yl)-2′H-spiro[chroman-4,5′-[1,2,4]oxadiazol]-3′-amine (10 mg, 30%). 1H-NMR (MeOD): 1.62 (m, 2H), 1.96 (m, 3H), 2.70 (m, 1H), 3.30 (s, 3H), 3.38 (m, 4H), 3.83 (m, 2H), 4.12 (m, 2H), 6.84 (m, 1H), 6.96 (m, 1H), 7.18 (m, 2H), 7.64 (m, 1H), 7.86 (d, 1H).

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-04d5b7ba1bdc4df7887550e62c447e84
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08921359B2

Reaction notes

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