2-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl → ethyl 3-(6-chloro-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-yl)propanoate

HRID 571416Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[CH:6][C:5]2[C:8]([CH:30]=[CH2:31])=[N:9][N:10]([C:11]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:4]=2[CH:3]=1.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.[Br-].[CH2:62]([O:64][C:65](=[O:69])CC[Zn+])[CH3:63]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:1][C:2]1[N:7]=[CH:6][C:5]2[C:8]([CH2:30][CH2:31][C:65]([O:64][CH2:62][CH3:63])=[O:69])=[N:9][N:10]([C:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:4]=2[CH:3]=1

Participants

Conditions

Temperature: 40 °C

Procedure

An oven-dried, nitrogen cooled 2 ml microwave vial was charged with 6-chloro-3-iodo-1-trityl-1H-pyrazolo[4,3-c]pyridine (Intermediate 3a, 103 mg, 0.197 mmol), palladium (II) acetate (2.2 mg, 9.80 μmol) and SPhos (8.2 mg, 0.020 mmol), sealed under an argon atmosphere, charged with (3-ethoxy-3-oxopropyl)zinc(II) bromide (0.5 M in THF, 0.5 ml, 0.250 mmol) and heated to 40° C. for 23 hr. Quenched with MeOH, filtered through celite, concentrated in vacuo and purified via flash chromatography (0-100% EtOAc/Hex). Obtained ethyl 3-(6-chloro-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-yl)propanoate (32.6 mg, 0.066 mmol, 33.3% yield) as a yellow residue. MS ESI calc'd for C30H26ClN3O2 [M+H]+=496, found 496.

Workup

temperatureAn oven-dried, nitrogen cooled 2 ml microwave vial
customsealed under an argon atmosphere
customQuenched with MeOH
filtrationfiltered through celite
concentrationconcentrated in vacuo
custompurified via flash chromatography (0-100% EtOAc/Hex)

Sources & evidence

ORD record: ord-1ffcc6dd3a6e453d8302e03547ba1355
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09023865B2

Reaction notes

Loading…