Triethylamine → HCID 68456536, compound

HRID 969897Notes

Reaction equation

HRID 969897 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][CH:13]=3)=[N:6][C:5]2=[C:14]([C:16]([OH:18])=O)[CH:15]=1.Cl.Cl.[NH2:21][C@H:22]1[CH:27]2[CH2:28][CH2:29][N:24]([CH2:25][CH2:26]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>[N:24]12[CH2:29][CH2:28][CH:27]([CH2:26][CH2:25]1)[C@H:22]([NH:21][C:16]([C:14]1[CH:15]=[C:2]([Cl:1])[CH:3]=[C:4]3[O:8][C:7]([C:9]4[S:10][CH:11]=[CH:12][CH:13]=4)=[N:6][C:5]=13)=[O:18])[CH2:23]2

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 12494973(3S)-1-azabicyclo[2.2.2]octan-3-amine dihydrochlorideHCID 68459737HCID 68459737, compound

Product 1

HCID 68456536HCID 68456536, compoundYield 31%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 6-chloro-2-(thiophen-2-yl)benzo[d]oxazole-4-carboxylic acid (70 mg, 0.25 mmol), (S)-(−)-3-aminoquinuclidine dihydrochloride (50 mg, 0.25 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (96 mg, 0.50 mmol) and 1-hydroxybenzotriazole (68 mg, 0.50 mmol) in DMF (2 mL) was stirred at room temperature for 5 min, then triethylamine (0.13 mL, 1.00 mmol) was added. The resulting reaction mixture was stirred at room temperature for 12 h. The mixture was diluted with dichloromethane (20 mL), then washed with a saturated solution of sodium bicarbonate (10 mL). The aqueous layer was further extracted with dichloromethane (3×15 mL). The combined organics were dried (Na2SO4), filtered and concentrated. The crude material was purified by column chromatography (silica gel, 89:10:1 dichloromethane/methanol/concentrated ammonium hydroxide) to afford (S)-N-(1-azabicyclo[2.2.2]oct-3-yl)-6-chloro-2-thiophen-2-ylbenzoxazole-4-carboxamide (30 mg, 31%) as a white solid: 1H NMR (500 MHz, CDCl3) δ 9.40 (d, J=7.5 Hz, 1H), 8.16 (d, J=2.0 Hz, 1H), 7.94 (dd, J=4.0, 1.5 Hz, 1H), 7.67-7.65 (m, 2H), 7.26-7.23 (m, 1H), 4.30-4.26 (m, 1H), 3.49 (ddd, J=11.5, 9.5, 2.0 Hz, 1H), 3.15-2.85 (m, 4H), 2.77 (dd, J=14.5, 3.5 Hz, 1H), 2.15-2.05 (m, 2H), 1.78-1.70 (m, 2H), 1.65-1.53 (m, 1H); MS (ESI+) m/z 388 (M+H); HPLC>99% (AUC), tR=13.84 min.

Workup

  1. customThe resulting reaction mixture
  2. stirringwas stirred at room temperature for 12 h
  3. washwashed with a saturated solution of sodium bicarbonate (10 mL)
  4. extractionThe aqueous layer was further extracted with dichloromethane (3×15 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, 89:10:1 dichloromethane/methanol/concentrated ammonium hydroxide)

Sources & evidence

ORD record
ord-097b9a863b4943d49d5b813e90e08f2a
Source dataset
uspto-grants-2007_12
Patent number
US07307094B2

Reaction notes

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