Piperidine → 5-methoxy-2-[1-(4-methoxybenzyl)-1H-indazol-3-yl]pyrimidin-4-amine

HRID 1776391Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:21]=[CH:20][C:6]([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([C:17](=[NH:19])[NH2:18])=[N:9]2)=[CH:5][CH:4]=1.C[N:23](C)[CH:24](N(C)C)[CH:25]([O:28][CH3:29])[C:26]#N.N1CCCCC1>CC(C)CCO>[CH3:29][O:28][C:25]1[C:24]([NH2:23])=[N:19][C:17]([C:10]2[C:11]3[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=3)[N:8]([CH2:7][C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:21][CH:20]=3)[N:9]=2)=[N:18][CH:26]=1

Participants

Conditions

Temperature: 100 °C

Procedure

6.45 g of 1-(4-methoxybenzyl)-1H-indazole-3-carboximidamide (23.0 mmol, 1 eq.), 5.40 g of 3,3-bis(dimethylamino)-2-methoxypropanenitrile (1-2-1, 31.5 mmol, 1.37 eq.) and 0.455 ml of piperidine (4.60 mmol, 0.2 eq.) were dissolved in 82.7 ml of dry 3-methylbutan-1-ol, put under a nitrogen atmosphere and stirred at 100° C. for 3 days. The mixture was cooled down at room temperature and stirred for 18 hours for crystallization. The resulting suspension was filtered off. The crystals were washed with cold methanol and dried in vacuo at 50° C. The crystallization was repeated twice with cold methanol to receive 2 further filter cakes and a combined yield of 6.87 g (19 mmol, 82.5%) of the analytically pure target compound.

Workup

temperatureThe mixture was cooled down at room temperature
stirringstirred for 18 hours for crystallization
filtrationThe resulting suspension was filtered off
washThe crystals were washed with cold methanol
customdried in vacuo at 50° C
customThe crystallization
filtrationfurther filter cakes

Sources & evidence

ORD record: ord-7cc7c822465145db94118cc8380baea6
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09265763B2

Reaction notes

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