Triethylamine → HCID 68454432, compound

HRID 506329Notes

Reaction equation

HRID 506329 reaction equation
[S:1]1[CH:5]=[C:4]([C:6]2[O:7][C:8]3[C:9](=[C:11]([C:15]([OH:17])=O)[CH:12]=[CH:13][CH:14]=3)[N:10]=2)[N:3]=[CH:2]1.[ClH:18].C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.Cl.Cl.[NH2:42][CH:43]1[CH2:50][CH:49]2[N:51]([CH3:52])[CH:45]([CH2:46][CH2:47][CH2:48]2)[CH2:44]1.C(N(CC)CC)C>CN(C=O)C.C(OCC)(=O)C>[ClH:18].[CH3:52][N:51]1[CH:45]2[CH2:46][CH2:47][CH2:48][CH:49]1[CH2:50][CH:43]([NH:42][C:15]([C:11]1[CH:12]=[CH:13][CH:14]=[C:8]3[O:7][C:6]([C:4]4[N:3]=[CH:2][S:1][CH:5]=4)=[N:10][C:9]=13)=[O:17])[CH2:44]2

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 189569979-Methyl-9-azabicyclo[3.3.1]nonan-3-amine;dihydrochlorideHCID 68456550HCID 68456550, compound

Product 1

HCID 68454432HCID 68454432, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 2-(thiazol-4-yl)benzoxazole-4-carboxylic acid (60 mg, 0.24 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (92 mg, 0.48 mmol), 1-hydroxybenzotriazole (65 mg, 0.48 mmol) and 3-amino-9-methyl-9-azabicyclo[3.3.1]nonane dihydrochloride (68 mg, 0.30 mmol) in DMF (2 mL) was stirred at room temperature for 10 min, then triethylamine (0.10 mL, 0.73 mmol) was added. The resulting reaction mixture was stirred at room temperature overnight. The mixture was diluted with ethyl acetate and then washed with a saturated solution of sodium bicarbonate. The aqueous layer was further extracted with dichloromethane (2×50 mL). The combined organic layers were washed with brine (2×25 mL), dried (Na2SO4), filtered and concentrated. The crude material was purified by column chromatography (silica gel, 90:9:1 dichloromethane/methanol/concentrated ammonium hydroxide) and recrystallization from acetonitrile to afford the desired product (51 mg, 56%) as a light yellow solid: 1H NMR (500 MHz, CDCl3) δ 9.14 (br s, 1H), 9.03 (d, J=2.0 Hz, 1H), 8.40 (d, J=2.0 Hz, 1H), 8.22 (dd, J=7.8, 1.0 Hz, 1H), 7.76 (dd, J=8.0, 0.9 Hz, 1H), 7.51 (t, J=7.9 Hz, 1H), 4.70-4.61 (m, 1H), 3.35-3.28 (m, 2H), 2.75-2.66 (m, 2H), 2.68 (s, 3H), 2.40-2.30 (m, 1H), 2.24-2.12 (m, 2H), 1.97-1.85 (m, 2H), 1.70-1.61 (m, 1H), 1.50-1.41 (m, 2H); MS (ESI+) m/z 383 (M+H).

Workup

  1. customThe resulting reaction mixture
  2. stirringwas stirred at room temperature overnight
  3. washwashed with a saturated solution of sodium bicarbonate
  4. extractionThe aqueous layer was further extracted with dichloromethane (2×50 mL)
  5. washThe combined organic layers were washed with brine (2×25 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude material was purified by column chromatography (silica gel, 90:9:1 dichloromethane/methanol/concentrated ammonium hydroxide) and recrystallization from acetonitrile

Sources & evidence

ORD record
ord-24aa76018bf74f3eab380b798b2c1842
Source dataset
uspto-grants-2010_08
Patent number
US07781430B2

Reaction notes

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