1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → tert-butyl N-[(3S)-1-[3-chloro-6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]pyrazin-2-yl]-3-piperidyl]carbamate

HRID 57936Notes

Reaction equation

[CH3:1][C:2]1[N:7]=[C:6]([C:8]2[N:13]=[CH:12][C:11]3[CH:14]=[N:15][NH:16][C:10]=3[CH:9]=2)[CH:5]=[N:4][CH:3]=1.Br[C:18]1[N:23]=[C:22]([N:24]2[CH2:29][CH2:28][CH2:27][C@H:26]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:25]2)[C:21]([Cl:38])=[N:20][CH:19]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:38][C:21]1[C:22]([N:24]2[CH2:29][CH2:28][CH2:27][C@H:26]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:35])([CH3:34])[CH3:36])[CH2:25]2)=[N:23][C:18]([N:16]2[C:10]3[CH:9]=[C:8]([C:6]4[CH:5]=[N:4][CH:3]=[C:2]([CH3:1])[N:7]=4)[N:13]=[CH:12][C:11]=3[CH:14]=[N:15]2)=[CH:19][N:20]=1

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 6-(6-methylpyrazin-2-yl)-1H-pyrazolo[4,3-c]pyridine (110 mg, 0.52 mmol), tert-butyl N-[(3S)-1-(6-bromo-3-chloro-pyrazin-2-yl)-3-piperidyl]carbamate (252 mg, 0.62 mmol), tris(dibenzylideneacetone)dipalladium(0) (47 mg, 0.052 mmol), xantphos (62 mg; 0.10 mmol), and sodium tert-butoxide (103 mg, 1.04 mmol) in toluene 5.0 mL was stirred at 110° C. 18 h. The reaction was filtered through celite. The crude product was purified by flash chromatography (EtOAc/Heptane eluted at 75% EtOAc) to give the desired product 112 mg 41% yield. MS (ESI) m/z: 523.2.

Workup

custom18 h
filtrationThe reaction was filtered through celite
customThe crude product was purified by flash chromatography (EtOAc/Heptane eluted at 75% EtOAc)

Sources & evidence

ORD record: ord-0f0223aaa8794e5cb5eafae29e32946b
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09434725B2

Reaction notes

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