Ammonia → Ammonium Hydroxide

HRID 1773883Notes

Reaction equation

HRID 1773883 reaction equation
[Cl:1][C:2]1[C:15]2[CH2:14][CH2:13][N:12]3[C:8](=[N:9][C:10](I)=[CH:11]3)[CH:7]([O:17][CH:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)[C:6]=2[CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[C:31]1(B(O)O)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.N>C1COCC1.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.Cl[Pd]Cl.[Fe+2].O>[NH4+:9].[OH-:17].[Cl:1][C:2]1[C:15]2[CH2:14][CH2:13][N:12]3[C:8](=[N:9][C:10]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)=[CH:11]3)[CH:7]([O:17][CH:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 222AmmoniaHCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 72694673HCID 72694673, compound

Product 2

HCID 14923Ammonium HydroxideHCID 72694880HCID 72694880, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 8-chloro-2-iodo-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene (example 78A) (35 mg, 0.08 mmole) in THF (1 mL) in a screw-capped vial under argon are added 1M solution of K2CO3 (0.4 ml, 0.4 mmole), PdCl2(dppf)2 (3.5 mg) and benzeneboronic acid (13 mg, 0.104 mmole). The reaction mixture is heated at 100° C. overnight. Water is added to the reaction mixture and pH adjusted to 9-10 by adding concentrated ammonia solution. The aqueous phase is extracted three times with CH2Cl2. The organic phase is dried over magnesium sulphate, filtered and the solvent is removed under reduced pressure. The residue is pre-purified by silica gel chromatography using (CH2Cl2:MeOH) (100:0) to (90:10) then (CH2Cl2:MeOH:NH4OH) (9:1:0.1) to give 8-chloro-4-(1-methylpiperidin-4-yloxy)-2-phenyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene. [M+H]+=408.2 and 410.0 35Cl/37Cl.

Workup

  1. extractionThe aqueous phase is extracted three times with CH2Cl2
  2. dry with materialThe organic phase is dried over magnesium sulphate
  3. filtrationfiltered
  4. customthe solvent is removed under reduced pressure
  5. customThe residue is pre-purified by silica gel chromatography

Sources & evidence

ORD record
ord-30250f42a54045a48798d12666257892
Source dataset
uspto-grants-2016_02
Patent number
US09255101B2

Reaction notes

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