Triethylamine → HCID 68456829, compound

HRID 506321Notes

Reaction equation

HRID 506321 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[O:8][C:7]([C:9]3[S:10][C:11]([CH3:14])=[CH:12][CH:13]=3)=[N:6][C:5]2=[C:15]([C:17]([OH:19])=O)[CH:16]=1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.Cl.Cl.[NH2:44][C@H:45]1[CH:50]2[CH2:51][CH2:52][N:47]([CH2:48][CH2:49]2)[CH2:46]1.C(N(CC)CC)C>CN(C=O)C.ClCCl>[N:47]12[CH2:52][CH2:51][CH:50]([CH2:49][CH2:48]1)[C@H:45]([NH:44][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][C:11]([CH3:14])=[CH:12][CH:13]=4)=[N:6][C:5]=13)=[O:19])[CH2:46]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 68459121HCID 68459121, compound

Product 1

HCID 68456829HCID 68456829, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 6-chloro-2-(5-methylthiophen-2-yl)benzoxazole-4-carboxylic acid (41 mg, 0.14 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (53 mg, 0.28 mmol), 1-hydroxybenzotriazole (38 mg, 0.28 mmol) and (S)-(−)-3-aminoquinuclidine dihydrochloride (35 mg, 0.17 mmol) in DMF (2 mL) was stirred at room temperature for 10 min, then triethylamine (0.08 mL, 0.56 mmol) was added. The resulting reaction mixture was stirred at room temperature for 4 h. 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 (2×25 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)-6-chloro-2-(5-methylthiophen-2-yl)benzoxazole-4-carboxamide (30 mg, 55%) as a white solid: 1H NMR (500 MHz, CDCl3) δ 9.43 (d, J=7.4 Hz, 1H), 8.12 (d, J=1.9 Hz, 1H), 7.74 (d, J=3.7 Hz, 1H), 7.64 (d, J=1.9 Hz, 1H), 6.90 (dd, J=3.7, 0.9 Hz, 1H), 4.33-4.29 (m, 1H), 3.54-3.47 (m, 1H), 3.15-3.03 (m, 2H), 2.95-2.90 (m, 2H), 2.85-2.79 (m, 1H), 2.61 (s, 3H), 2.15-2.05 (m, 2H), 1.86-1.76 (m, 2H), 1.75-1.65 (m, 1H); MS (ESI+) m/z 402 (M+H); HPLC>99% (AUC), tR=12.99 min.

Workup

  1. customThe resulting reaction mixture
  2. stirringwas stirred at room temperature for 4 h
  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 (2×25 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-b98dce6c0cb14e47b5801f50cda19572
Source dataset
uspto-grants-2010_08
Patent number
US07781430B2

Reaction notes

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