1,4'-Bipiperidine → 7-(1,4'-bipiperidin-1'-yl)-4-({3-chloro-4-[(1-methyl-1H-imidazole-2-yl)thio]phenyl}amino)-6-methoxyquinoline-3-carbonitrile

HRID 269770Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][C:22](F)=[C:23]([O:26][CH3:27])[CH:24]=3)[N:19]=[CH:18][C:17]=2[C:29]#[N:30])[CH:5]=[CH:6][C:7]=1[S:8][C:9]1[N:10]([CH3:14])[CH:11]=[CH:12][N:13]=1.[N:31]1([CH:37]2[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]2)[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1>CN1CCCC1=O>[N:31]1([CH:37]2[CH2:42][CH2:41][N:40]([C:22]3[CH:21]=[C:20]4[C:25]([C:16]([NH:15][C:4]5[CH:5]=[CH:6][C:7]([S:8][C:9]6[N:10]([CH3:14])[CH:11]=[CH:12][N:13]=6)=[C:2]([Cl:1])[CH:3]=5)=[C:17]([C:29]#[N:30])[CH:18]=[N:19]4)=[CH:24][C:23]=3[O:26][CH3:27])[CH2:39][CH2:38]2)[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1

Participants

Conditions

Temperature: 105 °C

Procedure

Following the procedure of Example 11, a mixture of 220 mg (0.5 mmol) of 4-[3-chloro-4-(1-methyl-1H-imidazole-2-ylsulfanyl)-phenylamino]-7-fluoro-6-methoxyquinoline-3-carbonitrile and 290mg (1.72 mmol) of 4-piperidinopiperidine in 1.5 mL of 1-methyl 2-pyrrolidinone is heated at 105° C. for 17 hours to yield the crude product. Purification by silica gel chromatography (gradient 94:6 methylene chloride/methanol to 89:10:1 methylene chloride/methanol/ammonium hydroxide) gives 193 mg of 7-(1,4′-bipiperidin-1′-yl)-4-({3-chloro-4-[(1-methyl-1H-imidazole-2-yl)thio]phenyl}amino)-6-methoxyquinoline-3-carbonitrile as a beige solid, mp 221-223° C.

Workup

customto yield the crude product
customPurification by silica gel chromatography (gradient 94:6 methylene chloride/methanol to 89:10:1 methylene chloride/methanol/ammonium hydroxide)

Sources & evidence

ORD record: ord-9541cc44b7f1480db7f49be700e4169a
Source dataset: uspto-grants-2008_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07449460B2

Reaction notes

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