Dimethylacetamide → HCID 66900310, compound

HRID 2044129Notes

Reaction equation

[C:1]([O:5][C:6](=[O:26])[NH:7][CH:8]([C:17]([N:19]1[CH2:24][CH2:23][CH:22]([CH3:25])[CH2:21][CH2:20]1)=[O:18])[CH2:9][CH2:10][N:11]1[C:15](Br)=[CH:14][CH:13]=[N:12]1)([CH3:4])([CH3:3])[CH3:2].C[C:28]([N:30](C)C)=O>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].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.[Fe+2].[C-]#N.[C-]#N.[Zn+2].[Zn]>[C:1]([O:5][C:6](=[O:26])[NH:7][CH:8]([C:17]([N:19]1[CH2:24][CH2:23][CH:22]([CH3:25])[CH2:21][CH2:20]1)=[O:18])[CH2:9][CH2:10][N:11]1[C:15]([C:28]#[N:30])=[CH:14][CH:13]=[N:12]1)([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 0.34 g (0.79 mmol) of [3-(5-bromo-pyrazol-1-yl)-1-(4-methyl-piperidine-1-carbonyl)-propyl]-carbamic acid tert-butyl ester (prepared in the synthesis of I-080), 31 mg (0.034 mmol) of Pd2(dba)3, 38 mg (0.069 mmol) of dppf, 96 mg (0.83 mmol) of Zn(CN)2, and 13 mg (0.20 mmol) of Zn powder in 2 mL of DMA is heated to 120° C. for 3 h in a pressure tube. The mixture is cooled, filtered, and purified directly on preparative HPLC to provide 0.22 g (74%) of [3-(5-cyano-pyrazol-1-yl)-1-(4-methyl-piperidine-1-carbonyl)-propyl]-carbamic acid tert-butyl ester. This material is then stirred in 2.5 mL of 4 M HCl in 1,4-dioxane for 1 h, and then concentrated to provide I-091.

Workup

temperatureThe mixture is cooled
filtrationfiltered
custompurified directly on preparative HPLC

Sources & evidence

ORD record: ord-314b81fb8d014f6ea00885f35ac828b7
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08586748B2

Reaction notes

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