5-Carbamoyl-4-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester → 4-[2-(2-Isopropyl-2H[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yl]-1,2,5,6-tetrahydro-pyridine-3-carboxylic acid amide

HRID 1629454Notes

Reaction equation

HRID 1629454 reaction equation
C(OC([N:8]1[CH2:13][C:12]([C:14](=[O:16])[NH2:15])=[C:11]([C:17]2[CH:38]=[CH:37][C:20]3[C:21]4[N:25]([CH2:26][CH2:27][O:28][C:19]=3[CH:18]=2)[CH:24]=[C:23]([C:29]2[N:30]([CH:34]([CH3:36])[CH3:35])[N:31]=[CH:32][N:33]=2)[N:22]=4)[CH2:10][CH2:9]1)=O)(C)(C)C.C(=O)([O-])[O-].C([N+](CC=C)(CC=C)CC=C)C=C.C([N+](CC=C)(CC=C)CC=C)C=C>C(O)(C(F)(F)F)=O.CO.C(Cl)Cl>[CH:34]([N:30]1[C:29]([C:23]2[N:22]=[C:21]3[N:25]([CH2:26][CH2:27][O:28][C:19]4[CH:18]=[C:17]([C:11]5[CH2:10][CH2:9][NH:8][CH2:13][C:12]=5[C:14]([NH2:15])=[O:16])[CH:38]=[CH:37][C:20]=43)[CH:24]=2)=[N:33][CH:32]=[N:31]1)([CH3:36])[CH3:35]

Participants

6

Reactant 2

HCID 582043545-Carbamoyl-4-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl esterHCID 87097461Tetra allylammonium carbonate

Product 1

HCID 582049604-[2-(2-Isopropyl-2H[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yl]-1,2,5,6-tetrahydro-pyridine-3-carboxylic acid amideYield 82%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×HCID 6422Trifluoroacetic acidSolvent

Procedure

5-Carbamoyl-4-[2-(2-isopropyl-2H[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester was stirred in TFA (1 mL) and DCM (2 mL) for 2 h. The reaction mixture was concentrated in vacuo and the residue triturated with diethyl ether to give a solid. The solid was then treated with tetra allylammonium carbonate (polymer bound) (1.84 g, 4.68 mmol) in methanol and DCM for 30 min. The resin was filtered off and the filtrate concentrated in vacuo to give 4-[2-(2-Isopropyl-2H[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yl]-1,2,5,6-tetrahydro-pyridine-3-carboxylic acid amide (0.40 g, 82%). 1H NMR 300 MHz (CDCl3) δ: 8.52-8.46 (1 H, m), 7.88 (1 H, s), 7.71-7.69 (1 H, m), 7.08 (1 H, dd, J=8.30, 1.82 Hz), 6.98 (1 H, d, J=1.79 Hz), 6.01-6.00 (1 H, m), 4.52-4.47 (4 H, m), 3.75 (2 H, s), 3.15 (2 H, t, J=5.82 Hz), 2.51 (2 H, m), 1.60 (6 H, d, J=6.62 Hz).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue triturated with diethyl ether
  3. customto give a solid
  4. filtrationThe resin was filtered off
  5. concentrationthe filtrate concentrated in vacuo

Sources & evidence

ORD record
ord-9ca004d055f54134aee96f483326f0e7
Source dataset
uspto-grants-2014_07
Patent number
US08785626B2

Reaction notes

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