Water → 3-(2-fluoropyridin-4-yl)-2-phenyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole

HRID 1890258Notes

Reaction equation

[C:1]1([C:7]2[C:8](I)=[C:9]3[CH2:14][CH2:13][CH2:12][N:10]3[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[F:16][C:17]1[CH:22]=[C:21](B2OC(C)(C)C(C)(C)O2)[CH:20]=[CH:19][N:18]=1.C([O-])([O-])=O.[Cs+].[Cs+].O>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:16][C:17]1[CH:22]=[C:21]([C:8]2[C:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[N:11][N:10]3[CH2:12][CH2:13][CH2:14][C:9]=23)[CH:20]=[CH:19][N:18]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of 1.00 g (3.22 mmol) of 2-(phenyl)-3-iodo-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole, 1.80 g (8.06 mmol) of 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine, 2.63 g (8.06 mmol) of Cs2CO3 and 526 mg (0.65 mmol) of Pd(dppf)Cl2 in 8 ml of THF is heated under argon at 60° C. for 16 h. 20 ml of water are added, and the reaction mixture is extracted with 3×50 ml of ethyl acetate. The combined organic phases are dried over MgSO4 and freed from the solvent under reduced pressure. Purification by column chromatography on silica gel (cyclohexane/ethyl acetate) gives 507 mg (57%) of the desired product; log P(HCOOH): 2.53; 1H-NMR (DMSO-d6): 8.10 (d, 1H), 7.40 (m, 5H), 7.07 (d, 1H), 6.85 (s, 1H), 4.19 (dd, 2H), 3.11 (dd, 2H), 2.62 (m, 2H).

Workup

extractionthe reaction mixture is extracted with 3×50 ml of ethyl acetate
dry with materialThe combined organic phases are dried over MgSO4
customPurification by column chromatography on silica gel (cyclohexane/ethyl acetate)

Sources & evidence

ORD record: ord-e2a6de323cfd4f8c9ba79768165840ce
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08507472B2

Reaction notes

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