Water → 3,4,5,6-Tetrahydro-3,10-diaza-benzo[e]azulene-1-carboxylic acid {2-[2-(tetrahydropyran-2-yloxy)-ethoxy]-pyridin-3-yl}amide

HRID 481075Notes

Reaction equation

HRID 481075 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH2:8][CH2:9][O:10][C:11]1[C:16]([NH2:17])=[CH:15][CH:14]=[CH:13][N:12]=1.C[Al](C)C.C([O:24][C:25]([C:27]1[C:36]2[C:35]3[N:37]=[CH:38][CH:39]=[CH:40][C:34]=3[CH2:33][CH2:32][CH2:31][C:30]=2[NH:29][CH:28]=1)=O)C.O>C(Cl)Cl>[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH2:8][CH2:9][O:10][C:11]1[C:16]([NH:17][C:25]([C:27]2[C:36]3[C:35]4[N:37]=[CH:38][CH:39]=[CH:40][C:34]=4[CH2:33][CH2:32][CH2:31][C:30]=3[NH:29][CH:28]=2)=[O:24])=[CH:15][CH:14]=[CH:13][N:12]=1

Participants

6

Reactant 4

HCID 962WaterHCID 16682925TrimethylaluminumHCID 206056123,4,5,6-Tetrahydro-3,10-diazabenzo[e]azulene-1-carboxylic acid ethyl esterHCID 223188362-[2-(Tetrahydropyran-2-yloxy)-ethoxy]pyridin-3-ylamine

Product 1

HCID 865883163,4,5,6-Tetrahydro-3,10-diaza-benzo[e]azulene-1-carboxylic acid {2-[2-(tetrahydropyran-2-yloxy)-ethoxy]-pyridin-3-yl}amideYield 97.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-[2-(tetrahydropyran-2-yloxy)-ethoxy]pyridin-3-ylamine (2.3 g, 9.7 mmol) in DCM (8 mL) is added AlMe3 (2M in toluene, 4.9 mL) at rt. After stirring at room temperature for 1 h, a solution of 3,4,5,6-tetrahydro-3,10-diazabenzo[e]azulene-1-carboxylic acid ethyl ester (500 mg, 1.95 mmol) in DCM (10 mL) is added. The mixture is refluxed overnight. On cooling, water (5 mL) is added, and the resulting mixture is extracted with DCM. The combined DCM extracts are dried and solvent removed. The residue is separated by column chromatography on silica gel (5% methanol in DCM) to give 850 mg of 3,4,5,6-tetrahydro-3,10-diaza-benzo[e]azulene-1-carboxylic acid {2-[2-(tetrahydropyran-2-yloxy)-ethoxy]-pyridin-3-yl}amide as an oil.

Workup

  1. temperatureThe mixture is refluxed overnight
  2. temperatureOn cooling
  3. extractionthe resulting mixture is extracted with DCM
  4. dry with materialThe combined DCM extracts are dried
  5. customsolvent removed
  6. customThe residue is separated by column chromatography on silica gel (5% methanol in DCM)

Sources & evidence

ORD record
ord-526baeee427b494ca58f6b1c9a4d97ff
Source dataset
uspto-grants-2003_11
Patent number
US06653471B2

Reaction notes

Loading…