1-Hydroxybenzotriazole → HCID 59017519, compound

HRID 506310Notes

Reaction equation

HRID 506310 reaction equation
[S:1]1[CH:5]=[CH:4][C:3]([C:6]2[O:7][C:8]3[C:9](=[C:11]([C:15]([OH:17])=O)[CH:12]=[CH:13][CH:14]=3)[N:10]=2)=[CH:2]1.Cl.Cl.[NH2:20][CH:21]1[CH2:28][CH:27]2[N:29]([CH3:30])[CH:23]([CH2:24][CH2:25][CH2:26]2)[CH2:22]1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C>[CH3:30][N:29]1[CH:23]2[CH2:24][CH2:25][CH2:26][CH:27]1[CH2:28][CH:21]([NH:20][C:15]([C:11]1[CH:12]=[CH:13][CH:14]=[C:8]3[O:7][C:6]([C:3]4[CH:4]=[CH:5][S:1][CH:2]=4)=[N:10][C:9]=13)=[O:17])[CH2:22]2

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 189569979-Methyl-9-azabicyclo[3.3.1]nonan-3-amine;dihydrochlorideHCID 68459718HCID 68459718, compound

Product 1

HCID 59017519HCID 59017519, compoundYield 41.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 2-thiophen-3-ylbenzoxazole-4-carboxylic acid (78 mg, 0.32 mmol), 3-amino-9-methyl-9-azabicyclo[3.3.1]nonane dihydrochloride (86 mg, 0.38 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (86 mg, 0.45 mmol) and 1-hydroxybenzotriazole (122 mg, 0.90 mmol) in DMF (5 mL) was stirred for 10 min at room temperature, then DIPEA (0.26 mL, 1.6 mmol) was added. The resulting reaction mixture was stirred at room temperature overnight. The mixture was diluted with ethyl acetate (20 mL), and then washed with a saturated solution of sodium bicarbonate. The aqueous layer was further extracted with ethyl acetate (2×50 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 then recrystallized from acetonitrile to afford N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-2-thiophen-3-ylbenzoxazole-4-carboxamide (51 mg, 41%) as an off-white solid: 1H NMR (500 MHz, CDCl3) δ 8.99 (d, J=7.0 Hz, 1H), 8.24 (d, J=1.5 Hz, 1H), 8.20 (d, J=7.5 Hz, 1H), 7.78 (d, J=5.0 Hz, 1H), 7.77 (d, J=7.5 Hz, 1H), 7.52-7.51 (m, 1H), 7.44 (t, J=7.5 Hz, 1H), 4.61-4.51 (m, 1H), 3.19-3.01 (m, 2H), 2.72-2.61 (m, 2H), 2.54 (s, 3H), 2.22-1.98 (m, 2H), 1.60-1.47 (m, 4H), 1.26-1.13 (m, 2H); MS (ESI+) m/z 382 (M+H); HPLC>99% (AUC), tR=13.40 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 ethyl acetate (2×50 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-974c8638e6cc4dbeb252256e5bc870ce
Source dataset
uspto-grants-2010_08
Patent number
US07781430B2

Reaction notes

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