Cesium carbonate → HCID 89923930, compound

HRID 921963Notes

Reaction equation

HRID 921963 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]([CH2:18][CH3:19])[CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)[C:5]2=[N:20][CH:21]=[C:22]([C:23]#[N:24])[N:4]2[N:3]=1.Br[C:26]1[C:27]([Cl:46])=[C:28]([NH:34][C@@H:35]2[CH2:40][CH2:39][N:38]([C:41]([O:43][CH3:44])=[O:42])[CH2:37][C@H:36]2[OH:45])[CH:29]=[C:30]([C:32]#[N:33])[CH:31]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:46][C:27]1[C:26]([NH:1][C:2]2[N:7]=[C:6]([N:8]([CH2:18][CH3:19])[CH2:9][C:10]3[CH:11]=[CH:12][C:13]([O:16][CH3:17])=[CH:14][CH:15]=3)[C:5]3=[N:20][CH:21]=[C:22]([C:23]#[N:24])[N:4]3[N:3]=2)=[CH:31][C:30]([C:32]#[N:33])=[CH:29][C:28]=1[NH:34][C@@H:35]1[CH2:40][CH2:39][N:38]([C:41]([O:43][CH3:44])=[O:42])[CH2:37][C@H:36]1[OH:45]

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 89922587HCID 89922587, compoundHCID 89922979HCID 89922979, compound

Product 1

HCID 89923930HCID 89923930, compoundYield 99.9%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
70 °C

Procedure

A oven-dried 10 ml microwave flask was loaded with 2-amino-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (16 mg, 0.049 mmol), (3R,4R)-methyl 4-((3-bromo-2-chloro-5-cyanophenyl)amino)-3-hydroxypiperidine-1-carboxylate (19 mg, 0.049 mmol), Pd(OAc)2 (3 mg, 0.013 mmol), XANTPHOS (8 mg, 0.014 mmol) and Cs2CO3 (50 mg, 0.153 mmol). The flask was evacuated and back-filled with nitrogen 4 times. 1,4-Dioxane (0.5 mL) was added and the flask was again evacuated and back-filled with nitrogen 4 times, then heated with stirring to 70° C. for 2 hours. The reaction is complete by LCMS analysis. The reaction mixture was diluted with EtOAc, washed with water, brine and dried over Na2SO4. The solvent removed to afford (3R,4R)-methyl 4-((2-chloro-5-cyano-3-((7-cyano-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)amino)-3-hydroxypiperidine-1-carboxylate (30.9 mg). The material was used as is.

Workup

  1. customThe flask was evacuated
  2. additionback-filled with nitrogen 4 times
  3. addition1,4-Dioxane (0.5 mL) was added
  4. customthe flask was again evacuated
  5. additionback-filled with nitrogen 4 times
  6. temperatureheated
  7. additionThe reaction mixture was diluted with EtOAc
  8. washwashed with water, brine
  9. dry with materialdried over Na2SO4
  10. customThe solvent removed

Sources & evidence

ORD record
ord-1db8dc634bdd4b3cb951ce937657a2fb
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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