Diisopropylethylamine → 1-(6-Benzyl-4,5-dimethyl-pyridazin-3-yl)-piperidine-4-carboxylic acid cyanomethyl-amide

HRID 1479971Notes

Reaction equation

[CH2:1]([C:8]1[N:13]=[N:12][C:11]([N:14]2[CH2:19][CH2:18][CH:17]([C:20]([OH:22])=O)[CH2:16][CH2:15]2)=[C:10]([CH3:23])[C:9]=1[CH3:24])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.CN(C(O[N:42]1N=[N:49][C:44]2C=CC=N[C:43]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.NCC#N>CN(C=O)C.CCOC(C)=O>[C:43]([CH2:44][NH:49][C:20]([CH:17]1[CH2:16][CH2:15][N:14]([C:11]2[N:12]=[N:13][C:8]([CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[C:9]([CH3:24])[C:10]=2[CH3:23])[CH2:19][CH2:18]1)=[O:22])#[N:42]

Participants

Conditions

Temperature: 25 °C

Procedure

To a solution of 1-(6-benzyl-4,5-dimethyl-pyridazin-3-yl)-piperidine-4-carboxylic acid (350 mg, 1.08 mmol) in DMF (10 mL) is added DIPEA (0.94 mL, 5.4 mmol) and HATU (490 mg, 1.29 mmol). After being stirred at 25° C., aminoacetonitrile hydrochloride (119 mg, 1.29 mmol) is added. The mixture is stirred for 2 h, and diluted with EtOAc (20 mL) and washed with H2O (3×10 mL). The organic layer is dried over Na2SO4, filtered and concentrated. The crude product is purified by chromatography (CH2Cl2/MeOH: 97%/3%) to give 1-(6-benzyl-4,5-dimethyl-pyridazin-3-yl)-piperidine-4-carboxylic acid cyanomethyl-amide (280 mg, 72%).

Workup

stirringThe mixture is stirred for 2 h
washwashed with H2O (3×10 mL)
dry with materialThe organic layer is dried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe crude product is purified by chromatography (CH2Cl2/MeOH: 97%/3%)

Sources & evidence

ORD record: ord-5a133d2b9b1c4422b0e909dcb9aaaa73
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09409871B2

Reaction notes

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