Triethylamine → HCID 68454346, compound

HRID 969906Notes

Reaction equation

HRID 969906 reaction equation
[CH3:1][C:2]1[S:6][C:5]([C:7]2[O:8][C:9]3[C:10](=[C:12]([C:16]([OH:18])=O)[CH:13]=[CH:14][CH:15]=3)[N:11]=2)=[CH:4][CH:3]=1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.Cl.Cl.[NH2:43][C@H:44]1[CH:49]2[CH2:50][CH2:51][N:46]([CH2:47][CH2:48]2)[CH2:45]1.C(N(CC)CC)C>CN(C=O)C.ClCCl>[N:46]12[CH2:51][CH2:50][CH:49]([CH2:48][CH2:47]1)[C@H:44]([NH:43][C:16]([C:12]1[CH:13]=[CH:14][CH:15]=[C:9]3[O:8][C:7]([C:5]4[S:6][C:2]([CH3:1])=[CH:3][CH:4]=4)=[N:11][C:10]=13)=[O:18])[CH2:45]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 68459183HCID 68459183, compound

Product 1

HCID 68454346HCID 68454346, compoundYield 13%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-(5-methylthiophen-2-yl)benzoxazole-4-carboxylic acid (106 mg, 0.41 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (156 mg, 0.82 mmol), 1-hydroxybenzotriazole (110 mg, 0.82 mmol) and (S)-(−)-3-aminoquinuclidine dihydrochloride (101 mg, 0.51 mmol) in DMF (3 mL) was stirred at room temperature for 10 min, then triethylamine (0.23 mL, 1.64 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 (2×50 mL). The combined organic layers were washed with brine (2×50 mL), dried (Na2SO4), filtered and concentrated. The crude material was purified by column chromatography (silica gel, 90:9:1 dichloromethane/methanol/concentrated ammonium hydroxide) and recrystallization from acetonitrile to afford (S)-N-(1-azabicyclo[2.2.2]oct-3-yl)-2-(5-methylthiophen-2-yl)benzoxazole-4-carboxamide (19 mg, 13%) as a light yellow solid: 1H NMR (500 MHz, CDCl3) δ 9.55 (d, J=7.4 Hz, 1H), 8.15 (dd, J=7.8, 0.9 Hz, 1H), 7.74 (d, J=3.7 Hz, 1H), 7.65 (dd, J=7.2, 1.0 Hz, 1H), 7.42 (t, J=7.9 Hz, 1H), 6.89 (dd, J=3.7, 1.0 Hz, 1H), 4.35-4.30 (m, 1H), 3.55-3.48 (m, 1H), 3.16-3.07 (m, 2H), 2.96-2.91 (m, 2H), 2.86-2.82 (m, 1H), 2.60 (s, 3H), 2.18-2.12 (m, 2H), 1.80-1.75 (m, 2H), 1.71-1.65 (m, 1H); MS (ESI+) m/z 368 (M+H); HPLC 98.0% (AUC), tR=12.40 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 (2×50 mL)
  5. washThe combined organic layers were washed with brine (2×50 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) and recrystallization from acetonitrile

Sources & evidence

ORD record
ord-37f3fe7de90944f6b22f20aa505c58d5
Source dataset
uspto-grants-2007_12
Patent number
US07307094B2

Reaction notes

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