Boron tribromide → 5-(1H-pyrazol-1-yl)-2-(6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)phenol

HRID 1027196Notes

Reaction equation

C[O:2][C:3]1[CH:8]=[C:7]([N:9]2[CH:13]=[CH:12][CH:11]=[N:10]2)[CH:6]=[CH:5][C:4]=1[C:14]1[N:19]=[N:18][C:17]([C:20]2[CH2:25][CH2:24][N:23](C(OC(C)(C)C)=O)[CH2:22][CH:21]=2)=[CH:16][CH:15]=1.B(Br)(Br)Br>C(Cl)Cl>[N:9]1([C:7]2[CH:6]=[CH:5][C:4]([C:14]3[N:19]=[N:18][C:17]([C:20]4[CH2:25][CH2:24][NH:23][CH2:22][CH:21]=4)=[CH:16][CH:15]=3)=[C:3]([OH:2])[CH:8]=2)[CH:13]=[CH:12][CH:11]=[N:10]1

Participants

Conditions

Temperature: -78 °C

Procedure

tert-Butyl 4-(6-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)pyridazin-3-yl)-5,6-dihydropyridine-1(2H)-carboxylate (50 mg, 0.12 mmol) was dissolved in DCM (0.6 mL). The solution was cooled to −78° C. and 1 M BBr3 in DCM (0.6 mL) was added dropwise. The resulting suspension was removed from the ice bath and stirred at RT overnight. The reaction was quenched with water, diluted with MeOH then adsorbed onto a MeOH conditioned SCX column. The column was washed several times (5-7 column volumes) with MeOH then eluted with 2 N NH3 in MeOH to provide the desired product, 5-(1H-pyrazol-1-yl)-2-(6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)phenol, (9.7 mg, 0.03 mmol, 25% yield). LCMS Rt=0.49 min, M+1=320.1 (LCMS method Q). 1H NMR (DMSO-d6) δ 8.64 (d, J=2.3 Hz, 1H), 8.52 (d, J=9.5 Hz, 1H), 8.19 (dd, J=9.0, 3.0 Hz, 2H), 7.80 (d, J=1.3 Hz, 1H), 7.43-7.61 (m, 2H), 6.89-7.03 (m, 1H), 6.52-6.66 (m, 1H), 3.56-3.73 (m, 2H), 3.02-3.15 (m, 2H), 2.66-2.74 (m, 2H).

Workup

customThe resulting suspension was removed from the ice bath
customThe reaction was quenched with water
additiondiluted with MeOH
washThe column was washed several times (5-7 column volumes) with MeOH
washthen eluted with 2 N NH3 in MeOH

Sources & evidence

ORD record: ord-5d604b8c7d834554b05446731d82d332
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08729263B2

Reaction notes

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