1,1-Dichloroethane → HCID 89923190, compound

HRID 921818Notes

Reaction equation

[Cl:1][C:2]1[C:7]([N:8]2[CH2:13][CH2:12][CH:11]3[NH:14][CH2:15][CH2:16][CH:10]3[CH2:9]2)=[CH:6][C:5]([C:17]#[N:18])=[CH:4][C:3]=1[NH:19][C:20]1[N:25]=[C:24]([N:26]([CH:36]2[CH2:38][CH2:37]2)CC2C=CC(OC)=CC=2)[C:23]2=[N:39][CH:40]=[C:41]([C:42]#[N:43])[N:22]2[N:21]=1.[CH3:44][CH:45]1[CH2:47][O:46]1.C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O.ClC(Cl)C>C(O)C.C1COCC1>[Cl:1][C:2]1[C:7]([N:8]2[CH2:13][CH2:12][CH:11]3[N:14]([CH2:44][CH:45]([OH:46])[CH3:47])[CH2:15][CH2:16][CH:10]3[CH2:9]2)=[CH:6][C:5]([C:17]#[N:18])=[CH:4][C:3]=1[NH:19][C:20]1[N:25]=[C:24]([NH:26][CH:36]2[CH2:37][CH2:38]2)[C:23]2=[N:39][CH:40]=[C:41]([C:42]#[N:43])[N:22]2[N:21]=1

Participants

Conditions

Temperature: 35 °C

Procedure

A mixture of 2-((2-chloro-5-cyano-3-(hexahydro-1H-pyrrolo[3,2-c]pyridin-5(6H)-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Example 443F, 29 mg, 0.049 mmol) and 2-(=/−)-methyloxirane (14.15 mg, 0.244 mmol) in ethanol (0.8 mL)/THF (0.2 mL) in a sealed 1-dram vial was heated at 80° C. overnight. A clear solution was observed and LCMS showed completion of reaction. Solvent was evaporated and to the crude intermediate were added anisole (0.027 ml, 0.244 mmol) and 25% TFA in dichloroethane (2 ml, 6.49 mmol) and the resulting solution was stirred at 35° C. overnight. Solvent was evaporated and the crude was purified by prep-HPLC to give the title compound (9.8 mg) as a white solid.

Workup

customcompletion of reaction
customSolvent was evaporated and to the crude intermediate
customSolvent was evaporated
customthe crude was purified by prep-HPLC

Sources & evidence

ORD record: ord-612b1585814d4eeb9dda5efe7c6e71b4
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09273057B2

Reaction notes

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