Triethylamine → HCID 11503076, compound

HRID 506285Notes

Reaction equation

HRID 506285 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[C:11](=[C:13]([C:17](O)=[O:18])[CH:14]=[CH:15][CH:16]=3)[N:12]=2)=[C:4]([O:20][CH3:21])[CH:3]=1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.Cl.Cl.[NH2:46][CH:47]1[CH2:54][CH:53]2[N:55]([CH3:56])[CH:49]([CH2:50][CH2:51][CH2:52]2)[CH2:48]1.C(N(CC)CC)C>CN(C=O)C.ClCCl>[CH3:56][N:55]1[CH:49]2[CH2:50][CH2:51][CH2:52][CH:53]1[CH2:54][CH:47]([NH:46][C:17]([C:13]1[CH:14]=[CH:15][CH:16]=[C:10]3[O:9][C:8]([C:5]4[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][C:4]=4[O:20][CH3:21])=[N:12][C:11]=13)=[O:18])[CH2:48]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 68456721HCID 68456721, compound

Product 1

HCID 11503076HCID 11503076, compoundYield 74.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-(4-chloro-2-methoxyphenyl)benzoxazole-4-carboxylic acid (95 mg, 0.31 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (119 mg, 0.62 mmol), 1-hydroxybenzotriazole (76 mg, 0.62 mmol) and 3-amino-9-methyl-9-azabicyclo[3.3.1]nonane dihydrochloride (89 mg, 0.39 mmol) in DMF (3 mL) was stirred at room temperature for 10 min, then triethylamine (0.18 mL, 1.25 mmol) was added. The resulting reaction mixture was stirred at room temperature overnight. The mixture was diluted with dichloromethane and then washed with a saturated solution of sodium bicarbonate. The aqueous layer was further extracted with dichloromethane (3×50 mL). The combined organic layers were washed with water (3×50 mL), brine (3×50 mL), dried (Na2SO4), filtered and concentrated. The crude material was purified by column chromatography (silica gel, 90:9:1 dichloromethane/methanol/concentrated ammonium hydroxide) to afford N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(4-chloro-2-methoxyphenyl)benzoxazole-4-carboxamide (102 mg, 67%) as a light yellow solid: 1H NMR (500 MHz, CDCl3) δ 9.17 (br s, 1H), 8.20 (dd, J=7.7, 0.8 Hz, 1H), 8.11 (d, J=8.4 Hz, 1H), 7.69 (dd, J=7.3, 0.9 Hz, 1H), 7.45 (t, J=4.0 Hz, 1H), 7.16-7.10 (m, 2H), 4.67-4.56 (m, 1H), 4.04 (s, 3H), 3.10-3.02 (m, 2H), 2.70-2.60 (m, 5H), 2.57 (s, 3H), 2.20-2.00 (m, 3H), 1.20-1.10 (m, 2H); MS (ESI+) m/z 440 (M+H); HPLC 98.7% (AUC), tR=14.10 min.

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 (3×50 mL)
  5. washThe combined organic layers were washed with water (3×50 mL), brine (3×50 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)

Sources & evidence

ORD record
ord-f30f3836fdff4049bbf558a96e63bdc8
Source dataset
uspto-grants-2010_08
Patent number
US07781430B2

Reaction notes

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