Cesium carbonate → HCID 89923886, compound

HRID 921938Notes

Reaction equation

HRID 921938 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]([CH:18]2[CH2:20][CH2:19]2)CC2C=CC(OC)=CC=2)[C:5]2=[N:21][CH:22]=[C:23]([C:24]#[N:25])[N:4]2[N:3]=1.[NH2:26][C:27]1[C:28]([Cl:51])=[C:29]([N:35]2[CH2:43][C@H:42]3[C@H:37]([N:38](C(OC(C)(C)C)=O)[CH2:39][CH2:40][CH2:41]3)[CH2:36]2)[CH:30]=[C:31]([C:33]#[N:34])[CH:32]=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+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[Cl:51][C:28]1[C:29]([N:35]2[CH2:43][C@H:42]3[C@H:37]([NH:38][CH2:39][CH2:40][CH2:41]3)[CH2:36]2)=[CH:30][C:31]([C:33]#[N:34])=[CH:32][C:27]=1[NH:26][C:2]1[N:7]=[C:6]([NH:8][CH:18]2[CH2:19][CH2:20]2)[C:5]2=[N:21][CH:22]=[C:23]([C:24]#[N:25])[N:4]2[N:3]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 867084772-Chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrileHCID 118253456HCID 118253456, compound

Product 1

HCID 89923886HCID 89923886, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (395 mg, 1.114 mmol), (4aS,7aS)-tert-butyl 6-(3-amino-2-chloro-5-cyanophenyl)octahydro-1H-pyrrolo[3,4-b]pyridine-1-carboxylate (420 mg, 1.114 mmol), palladium(II) acetate (66.3 mg, 0.295 mmol), XANTPHOS (64.5 mg, 0.111 mmol), DPPF (61.8 mg, 0.111 mmol) and cesium carbonate (944 mg, 2.90 mmol) in Dioxane (7 ml) was evacuated and back filled with nitrogen three time and was heated at 80° C. for 5 h. The reaction mixture was filtered through a celite pad and the filtrate was concentrated. The crude product was purified by flash chromatography on silica gel using an automated ISCO system 40 g column, eluting with 0-5% MeOH in DCM (+/−)-(4aS,7aS)-tert-butyl (6-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)octahydro-1H-pyrrolo[3,4-b]pyridine-1-carboxylate (379 mg) was obtained as a brown solid.

Workup

  1. customwas evacuated
  2. additionback filled with nitrogen three time
  3. filtrationThe reaction mixture was filtered through a celite pad
  4. concentrationthe filtrate was concentrated
  5. customThe crude product was purified by flash chromatography on silica gel using an automated ISCO system 40 g column
  6. washeluting with 0-5% MeOH in DCM (+/−)-(4aS,7aS)-tert-butyl (6-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)octahydro-1H-pyrrolo[3,4-b]pyridine-1-carboxylate (379 mg)
  7. customwas obtained as a brown solid

Sources & evidence

ORD record
ord-f2dee5cdd68940bca3c53bb458509804
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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