1-tert-butyl-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → tert-butyl 4-(6-(6-(1-tert-butyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)-1,4-diazepane-1-carboxylate

HRID 57847Notes

Reaction equation

[C:1]([N:5]1[CH:9]=[C:8](B2OC(C)(C)C(C)(C)O2)[CH:7]=[N:6]1)([CH3:4])([CH3:3])[CH3:2].Cl[C:20]1[N:25]=[CH:24][C:23]2[CH:26]=[N:27][N:28]([C:29]3[N:34]=[C:33]([N:35]4[CH2:41][CH2:40][CH2:39][N:38]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:37][CH2:36]4)[CH:32]=[CH:31][CH:30]=3)[C:22]=2[CH:21]=1>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+].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]>[C:1]([N:5]1[CH:9]=[C:8]([C:20]2[N:25]=[CH:24][C:23]3[CH:26]=[N:27][N:28]([C:29]4[N:34]=[C:33]([N:35]5[CH2:41][CH2:40][CH2:39][N:38]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:37][CH2:36]5)[CH:32]=[CH:31][CH:30]=4)[C:22]=3[CH:21]=2)[CH:7]=[N:6]1)([CH3:2])([CH3:3])[CH3:4]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 1-tert-butyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (220 mg, 0.88 mmol), tert-butyl 4-(6-(6-chloro-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)-1,4-diazepane-1-carboxylate (377 mg, 0.88 mmol), and Pd(dppf)Cl2 (64 mg, 0.088 mmol) in 1,4-dioxane (20 mL) and Na2CO3 (2.0 M, 5 mL) under nitrogen was heated at 100° C. for 20 hours. The crude product was purified by silica gel chromatography using petroleum ether:EtOAc (50%-100%) as eluting solvents to afford tert-butyl 4-(6-(6-(1-tert-butyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)-1,4-diazepane-1-carboxylate as a yellow solid (240 mg, 53%). MS (ESI) m/z: 517 [M+H]+.

Workup

customThe crude product was purified by silica gel chromatography
washEtOAc (50%-100%) as eluting solvents

Sources & evidence

ORD record: ord-274c87d39a6e4be2b78c1c38aa1afcec
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09434725B2

Reaction notes

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