Triethylamine → HCID 59017512, compound

HRID 969905Notes

Reaction equation

HRID 969905 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[O:8][C:7]([C:9]3[S:10][CH:11]=[CH:12][C:13]=3[Cl:14])=[N:6][C:5]2=[C:15]([C:17]([OH:19])=O)[CH:16]=1.Cl.Cl.[NH2:22][CH:23]1[CH2:30][CH:29]2[N:31]([CH3:32])[CH:25]([CH2:26][CH2:27][CH2:28]2)[CH2:24]1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C=O)C.ClCCl>[CH3:32][N:31]1[CH:25]2[CH2:26][CH2:27][CH2:28][CH:29]1[CH2:30][CH:23]([NH:22][C:17]([C:15]1[CH:16]=[C:2]([Cl:1])[CH:3]=[C:4]3[O:8][C:7]([C:9]4[S:10][CH:11]=[CH:12][C:13]=4[Cl:14])=[N:6][C:5]=13)=[O:19])[CH2:24]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 68458893HCID 68458893, compound

Product 1

HCID 59017512HCID 59017512, compoundYield 37%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 6-chloro-2-(3-chlorothiophen-2-yl)benzoxazole-4-carboxylic acid (67 mg, 0.21 mmol), 3-amino-9-methyl-9-azabicyclo[3.3.1]nonane dihydrochloride (57 mg, 0.25 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (80 mg, 0.42 mmol) and 1-hydroxybenzotriazole (57 mg, 0.42 mmol) in DMF (5 mL) was stirred at room temperature, then triethylamine (0.15 mL, 1.05 mmol) was added. The resulting reaction mixture was stirred at room temperature overnight. The mixture was diluted with dichloromethane (30 mL), and then washed with a saturated solution of sodium bicarbonate. The aqueous layer was further extracted with dichloromethane (2×30 mL). The combined organics were dried (Na2SO4), filtered and concentrated. The crude material was purified by column chromatography (silica gel, 90:9:1 ethyl acetate/methanol/concentrated ammonium hydroxide) and recrystallized from acetonitrile to afford N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-6-chloro-2-(3-chlorothiophen-2-yl)benzoxazole-4-carboxamide (35 mg, 37%) as a white solid: 1H NMR (500 MHz, CDCl3) δ 9.01 (d, J=6.0 Hz, 1H), 8.20 (d, J=2.0 Hz, 1H), 7.70 (d, J=1.5 Hz, 1H), 7.61 (d, J=5.5 Hz, 1H), 7.17 (d, J=5.0 Hz, 1H), 4.63-4.53 (m, 1H), 3.24-3.13 (m, 2H), 2.70-2.55 (m, 5H), 2.12-2.00 (m, 3H), 1.64-1.48 (m, 3H), 1.28-1.12 (m, 2H); MS (ESI+) m/z 450 (M+H); HPLC>99% (AUC), tR=13.32 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 (2×30 mL)
  5. dry with materialThe combined organics were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was purified by column chromatography (silica gel, 90:9:1 ethyl acetate/methanol/concentrated ammonium hydroxide)
  9. customrecrystallized from acetonitrile

Sources & evidence

ORD record
ord-ef341cc1c6bc44f2b107e0b9ed49d904
Source dataset
uspto-grants-2007_12
Patent number
US07307094B2

Reaction notes

Loading…