Triethylamine → HCID 11690373, compound

HRID 506289Notes

Reaction equation

HRID 506289 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]([OH:19])=O)[CH:14]=[CH:15][CH:16]=3)[N:12]=2)=[C:4]([CH3:20])[CH:3]=1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.Cl.Cl.[NH2:45][CH:46]1[CH2:53][CH:52]2[N:54]([CH3:55])[CH:48]([CH2:49][CH2:50][CH2:51]2)[CH2:47]1.C(N(CC)CC)C>CN(C=O)C.ClCCl>[CH3:55][N:54]1[CH:48]2[CH2:49][CH2:50][CH2:51][CH:52]1[CH2:53][CH:46]([NH:45][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[CH3:20])=[N:12][C:11]=13)=[O:19])[CH2:47]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 68456664HCID 68456664, compound

Product 1

HCID 11690373HCID 11690373, compoundYield 22%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-(4-chloro-2-methylphenyl)benzoxazole-4-carboxylic acid (59 mg, 0.21 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (79 mg, 0.41 mmol), 1-hydroxybenzotriazole (55 mg, 0.41 mmol) and 3-amino-9-methyl-9-azabicyclo[3.3.1]nonane dihydrochloride (72 mg, 0.26 mmol) in DMF (3 mL) was stirred at room temperature for 10 min, then triethylamine (0.11 mL, 0.82 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 (2×20 mL). The combined organic layers were washed with water (2×20 mL), brine (2×20 mL), dried (Na2SO4), filtered and concentrated. The crude material was purified by preparative TLC (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-methylphenyl)benzoxazole-4-carboxamide (19 mg, 22%) as a light yellow solid: 1H NMR (500 MHz, CDCl3) δ 9.01 (br s, 1H), 8.22 (dd, J=7.8, 1.0 Hz, 1H), 8.18 (d, J=8.4 Hz, 1H), 7.71 (dd, J=8.1, 0.9 Hz, 1H), 7.49 (t, J=7.9 Hz, 1H), 7.43-7.36 (m, 2H), 4.67-4.60 (m, 1H), 3.25-3.15 (m, 2H), 2.88 (s, 3H), 2.70-2.55 (m, 2H), 2.48 (s, 3H), 2.10-2.00 (m, 3H), 1.65-1.40 (m, 3H), 1.20-1.10 (m, 2H); MS (ESI+) m/z 424 (M+H); HPLC 98.4% (AUC), tR=13.82 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 (2×20 mL)
  5. washThe combined organic layers were washed with water (2×20 mL), brine (2×20 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude material was purified by preparative TLC (silica gel, 90:9:1 dichloromethane/methanol concentrated ammonium hydroxide)

Sources & evidence

ORD record
ord-4e410e9111ae4342988cc718daf3ccd5
Source dataset
uspto-grants-2010_08
Patent number
US07781430B2

Reaction notes

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