4-Hydroxymethylpyridine → 4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-7-(pyridin-4-ylmethoxy)-quinoline

HRID 8282

Reaction equation

[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[C:8]([C:15]2[C:24]3[C:19](=[CH:20][C:21]([OH:25])=[CH:22][CH:23]=3)[N:18]=[CH:17][CH:16]=2)=[C:9]2[CH2:14][CH2:13][CH2:12][N:10]2[N:11]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N:45]1[CH:50]=[CH:49][C:48]([CH2:51]O)=[CH:47][CH:46]=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1(C)C=CC=CC=1.O1CCCC1>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[C:8]([C:15]2[C:24]3[C:19](=[CH:20][C:21]([O:25][CH2:51][C:48]4[CH:49]=[CH:50][N:45]=[CH:46][CH:47]=4)=[CH:22][CH:23]=3)[N:18]=[CH:17][CH:16]=2)=[C:9]2[CH2:14][CH2:13][CH2:12][N:10]2[N:11]=1

Participants

Conditions

Temperature: 75 °C

Procedure

4-(2-Pyridin-2-yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-quinolin-7-ol (0.100 g, 0.305 mmol), triphenylphosphine (0.080 g, 0.305 mmol), and 4-pyridylcarbinol (0.033 g, 0.305 mmol) are combined in toluene (1.0 mL) and treated with diisopropylazodicarboxylate (0.062 g, 0.305 mmol). The resulting mixture is heated at 75° C. for 18 hours. The mixture is diluted with tetrahydrofuran and heated at 75° C. for 24 h. The mixture is placed on a 10 g SCX resin column which is washed sequentially with dichloromethane (120 mL), methanol (60 mL), and 4:1 dichloromethane/2 N ammonia in methanol (125 mL). The latter fraction is concentrated in vacuo and the residue chromatographed on SiO2 (9:1 ethyl acetate:2N ammonia in methanol) to yield the desired product as a tan solid, 0.035 g (27%).

Workup

temperatureheated at 75° C. for 24 h
washis washed sequentially with dichloromethane (120 mL), methanol (60 mL), and 4:1 dichloromethane/2 N ammonia in methanol (125 mL)
concentrationThe latter fraction is concentrated in vacuo
customthe residue chromatographed on SiO2 (9:1 ethyl acetate:2N ammonia in methanol)

Sources & evidence

ORD record: ord-3083cd80a9114d2db6dad12c4718d638
Source dataset: uspto-grants-2006_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07087626B2

Linked notes

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