Triethylamine → HCID 58204406, compound

HRID 1498504Notes

Reaction equation

HRID 1498504 reaction equation
C[O:2][C:3](=O)[CH:4]([CH3:28])[CH2:5][C:6]1[CH:27]=[CH:26][C:9]2[C:10]3[N:14]([CH2:15][CH2:16][O:17][C:8]=2[CH:7]=1)[CH:13]=[C:12]([C:18]1[N:19]([CH:23]([CH3:25])[CH3:24])[N:20]=[CH:21][N:22]=1)[N:11]=3.O.[OH-].[Li+].C[N:34](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Cl-].[NH4+].C(N(CC)CC)C>CO.O>[CH:23]([N:19]1[C:18]([C:12]2[N:11]=[C:10]3[C:9]4[CH:26]=[CH:27][C:6]([CH2:5][CH:4]([CH3:28])[C:3]([NH2:34])=[O:2])=[CH:7][C:8]=4[O:17][CH2:16][CH2:15][N:14]3[CH:13]=2)=[N:22][CH:21]=[N:20]1)([CH3:25])[CH3:24]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 168937Lithium hydroxide, monohydrateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67050715HCID 67050715, compound

Product 1

HCID 58204406HCID 58204406, compoundYield 42.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
45 °C

Procedure

To a solution of 3-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yl]-2-methyl-propionic acid methyl ester (150 mg, 0.38 mmol) in methanol (5 mL) and H2O (0.5 mL) was added lithium hydroxide monohydrate (30 mg, 0.76 mmol) and the reaction mixture heated at 45° C. for 72 h. The reaction mixture was concentrated in vacuo and the residue azeotroped with acetonitrile (3×10 mL). The resultant residue was suspended in DMF (3 mL) and HATU (289 mg, 0.76 mmol), ammonium chloride (61 mg, 1.14 mmol) and triethylamine (159 μL, 1.14 mmol) added. The reaction mixture was stirred at RT for 30 min. The mixture was diluted with water (15 mL) and extracted with ethyl acetate (2×10 mL). The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, eluting with 0-10% methanol in DCM) to yield 435 as a white solid (61 mg, 42%). LCMS: RT=7.27 min, [M+H]+=381. 1H NMR 400 MHz δ (DMSO-d6): 8.25 (1H, d, J=8.4 Hz), 7.86 (1H, s), 7.85 (1H, s), 7.21 (1H, br s), 6.93 (1H, dd, J=8.4, 1.8 Hz), 6.83 (1H, d, J=1.8 Hz), 6.66 (1H, br s), 5.85 (1H, sept, J=6.7 Hz), 4.50-4.39 (4H, m), 2.86-2.74 (1H, m), 2.56-2.42 (2H, m), 1.44 (6H, d, J=6.7 Hz), 0.97 (3H, d, J=6.6 Hz)

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue azeotroped with acetonitrile (3×10 mL)
  3. extractionextracted with ethyl acetate (2×10 mL)
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. washThe resultant residue was subjected to flash chromatography (SiO2, eluting with 0-10% methanol in DCM)

Sources & evidence

ORD record
ord-d9732bcbbe9b4292892175d7339955bb
Source dataset
uspto-grants-2015_12
Patent number
US09198918B2

Reaction notes

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