Potassium Carbonate → 6-(5-Chloropyridin-3-yl)-5'-methylspiro[chroman-4,2'-imidazol]-4'-amine

HRID 539318Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:11]3([N:15]=[C:14]([NH2:16])[C:13]([CH3:17])=[N:12]3)[CH2:10][CH2:9][O:8][C:5]2=[CH:6][CH:7]=1.[Cl:18][C:19]1[CH:20]=[C:21](B(O)O)[CH:22]=[N:23][CH:24]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[Cl:18][C:19]1[CH:20]=[C:21]([C:2]2[CH:3]=[C:4]3[C:11]4([N:15]=[C:14]([NH2:16])[C:13]([CH3:17])=[N:12]4)[CH2:10][CH2:9][O:8][C:5]3=[CH:6][CH:7]=2)[CH:22]=[N:23][CH:24]=1

Participants

Conditions

Temperature: 130 °C

Procedure

6-Bromo-5′-methylspiro[chroman-4,2′-imidazol]-4′-amine (60 mg, 0.20 mmol, Intermediate 4), 5-chloropyridin-3-ylboronic acid (62 mg, 0.40 mmol) and 2M K2CO3 (aq, 0.20 mL, 0.41 mmol) were mixed in dioxane (5 mL) and degassed by passing nitrogen through for 5 min. Then (1,1′-bis(diphenylphosphino)ferrocene)-dichloropalladium(II) (8 mg, 10 μmol) was added and the mixture was heated in a microwave oven at 130° C. for 1 h. Purification by preparative chromatography HPLC gave the title compound (42 mg, 63% yield): 1H NMR (400 MHz, CDCl3) δ ppm 2.17 (m, 2 H), 2.37 (s, 3 H), 4.59 (m, 2 H), 5.04 (br s, 2 H), 6.73 (d, 1 H), 7.01 (d, 1 H), 7.34 (dd, 1 H), 7.70 (m, 1 H), 8.45 (m, 1 H), 8.55 (m, 1 H); MS (ES+) m/z 327 [M+H]+.

Workup

customdegassed
customthrough for 5 min
customPurification by preparative chromatography HPLC

Sources & evidence

ORD record: ord-8018cd3311a54020b1ab72afc0ba0527
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08865911B2

Reaction notes

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