Triethylamine → HCID 11633989, compound

HRID 506316Notes

Reaction equation

HRID 506316 reaction equation
[Br:1][C:2]1[CH:6]=[CH:5][S:4][C:3]=1[C:7]1[O:8][C:9]2[C:10](=[C:12]([C:16]([OH:18])=O)[CH:13]=[CH:14][CH:15]=2)[N:11]=1.Cl.Cl.[NH2:21][CH:22]1[CH2:29][CH:28]2[N:30]([CH3:31])[CH:24]([CH2:25][CH2:26][CH2:27]2)[CH2:23]1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C=O)C.ClCCl>[CH3:31][N:30]1[CH:24]2[CH2:25][CH2:26][CH2:27][CH:28]1[CH2:29][CH:22]([NH:21][C:16]([C:12]1[CH:13]=[CH:14][CH:15]=[C:9]3[O:8][C:7]([C:3]4[S:4][CH:5]=[CH:6][C:2]=4[Br:1])=[N:11][C:10]=13)=[O:18])[CH2:23]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 68455410HCID 68455410, compound

Product 1

HCID 11633989HCID 11633989, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-(3-bromothiophen-2-yl)benzoxazole-4-carboxylic acid (188 mg, 0.58 mmol), 3-amino-9-methyl-9-azabicyclo[3.3.1]nonane dihydrochloride (159 mg, 0.70 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (222 mg, 1.16 mmol) and 1-hydroxybenzotriazole (157 mg, 1.16 mmol) in DMF (3 mL) was stirred at room temperature for 10 min, then triethylamine (0.40 mL, 2.9 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)-2-(3-bromothiophen-2-yl)benzoxazole-4-carboxamide (199 mg, 75%) as a white solid: 1H NMR (500 MHz, CDCl3) δ 9.11 (d, J=6.5 Hz, 1H), 8.22 (dd, J=7.5, 1.0 Hz, 1H), 7.70 (d, J=8.0 Hz, 1H), 7.58 (d, J=5.5 Hz, 1H), 7.48 (t, J=8.0 Hz, 1H), 7.24 (d, J=5.5 Hz, 1H), 4.68-4.59 (m, 1H), 3.22-3.13 (m, 2H), 2.70-2.55 (m, 5H), 2.13-1.98 (m, 3H), 1.63-1.49 (m, 3H), 1.26-1.12 (m, 2H); MS (ESI+) m/z 460 (M+H); HPLC>99% (AUC), tR=13.09 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-7409df86ba1b4d11890e3524f2cd382c
Source dataset
uspto-grants-2010_08
Patent number
US07781430B2

Reaction notes

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