Triethylamine → HCID 67050789, compound

HRID 886456Notes

Reaction equation

HRID 886456 reaction equation
C(O[C:4](=[O:30])[C@H:5]([O:7][C:8]1[N:29]=[CH:28][C:11]2[C:12]3[N:16]([CH2:17][CH2:18][O:19][C:10]=2[CH:9]=1)[CH:15]=[C:14]([C:20]1[N:21]([CH:25]([CH3:27])[CH3:26])[N:22]=[CH:23][N:24]=1)[N:13]=3)[CH3:6])C.O.[OH-].[Li+].C[N:35](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.C(OCC)(=O)C>[CH:25]([N:21]1[C:20]([C:14]2[N:13]=[C:12]3[C:11]4[CH:28]=[N:29][C:8]([O:7][C@H:5]([CH3:6])[C:4]([NH2:35])=[O:30])=[CH:9][C:10]=4[O:19][CH2:18][CH2:17][N:16]3[CH:15]=2)=[N:24][CH:23]=[N:22]1)([CH3:27])[CH3:26]

Participants

9

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 58204963HCID 58204963, compound

Product 1

HCID 67050789HCID 67050789, compoundYield 43%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of (R)-2-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a,9-triaza-benzo[e]azulen-8-yloxy]-propionic acid ethyl ester (70 mg, 0.17 mmol) in methanol (5 mL) and water (1 mL) was added lithium hydroxide monohydrate (23 mg, 0.58 mmol) and the reaction mixture stirred at 50° C. for 1 h. The reaction mixture was concentrated in vacuo and the resultant residue azeotroped with acetonitrile (3×20 mL). The residue was dissolved in DMF (3 mL), HATU (220 mg, 0.58 mmol), ammonium chloride (46 mg, 0.86 mmol) and triethylamine (120 μL, 0.86 mmol) added and the reaction mixture stirred at RT for 1.5 h. The reaction mixture was diluted with ethyl acetate, washed with water, extracting with ethyl acetate (3×15 mL). The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. The residue was subjected to reverse phase preparative HPLC (C-18, 10-90% MeCN in water 0.1% formic acid, 25 min gradient) to yield 446 as a white solid (28 mg, 43%). LCMS: RT=3.07 min, [M+H]+=384; 1H NMR (400 MHz, d6-DMSO) 9.05 (1H, s), 7.87 (1H, s), 7.86 (1H, s), 7.38 (1H, br s), 7.05 (1H, br s), 6.41 (1H, s), 5.87 (1H, sept, J=6.6 Hz), 5.17 (1H, q, J=6.8 Hz), 4.60-4.43 (4H, m), 1.50-1.34 (9H, m)

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe resultant residue azeotroped with acetonitrile (3×20 mL)
  3. dissolutionThe residue was dissolved in DMF (3 mL)
  4. stirringthe reaction mixture stirred at RT for 1.5 h
  5. washwashed with water
  6. extractionextracting with ethyl acetate (3×15 mL)
  7. washThe combined organic extracts were washed with brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customphase preparative HPLC (C-18, 10-90% MeCN in water 0.1% formic acid, 25 min gradient)

Sources & evidence

ORD record
ord-eb10979099a0473db57ba7ef733c74cb
Source dataset
uspto-grants-2012_08
Patent number
US08242104B2

Reaction notes

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