1-Hydroxybenzotriazole → N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-6-chloro-2-phenylbenzoxazole-4-carboxamide

HRID 506229Notes

Reaction equation

HRID 506229 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[O:8][C:7]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)=[N:6][C:5]2=[C:15]([C:17]([OH:19])=O)[CH:16]=1.Cl.Cl.[NH2:22][CH:23]1[CH2:30][CH:29]2[N:31]([CH3:32])[CH:25]([CH2:26][CH2:27][CH2:28]2)[CH2:24]1.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[CH3:32][N:31]1[CH:25]2[CH2:26][CH2:27][CH2:28][CH:29]1[CH2:30][CH:23]([NH:22][C:17]([C:15]1[CH:16]=[C:2]([Cl:1])[CH:3]=[C:4]3[O:8][C:7]([C:9]4[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=4)=[N:6][C:5]=13)=[O:19])[CH2:24]2

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 189569979-Methyl-9-azabicyclo[3.3.1]nonan-3-amine;dihydrochlorideHCID 684576406-Chloro-2-phenyl-benzoxazole-4-carboxylic acid

Product 1

HCID 11675918N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-6-chloro-2-phenylbenzoxazole-4-carboxamideYield 14.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A 15-mL, round bottomed flask equipped with a magnetic stirrer was purged with nitrogen and charged with 6-chloro-2-phenyl-benzoxazole-4-carboxylic acid (0.075 g, 0.274 mmol), 3-amino-9-methyl-9-azabicyclo[3.3.1]nonane dihydrochloride (0.063 g, 0.411 mmol) 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide hydrochloride (0.079 g, 0.411 mmol), 1-hydroxybenzotriazole (0.037 g, 0.274 mmol), diisopropylethylamine (0.141 g, 1.09 mmol), and DMF (1.0 mL). After stirring at ambient temperature for 18 h, the reaction was concentrated under reduced pressure and purified by preparative HPLC to afford 0.016 g (14% yield) of N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-6-chloro-2-phenylbenzoxazole-4-carboxamide as an off-white solid: 1H NMR (500 MHz, CDCl3) δ 8.95 (br s, 1H), 8.23 (d, J=6.9 Hz, 2H), 8.20 (d, J=2.0 Hz, 1H), 7.71 (d, J=2.0 Hz, 1H), 7.65-7.57 (m, 3H), 4.58 (q, J=7.1 Hz, 1H), 3.18 (br s, 2H), 2.58 (m, 5H), 2.25-2.02 (m, 3H), 1.55 (s, 3H), 1.23 (m, 3H); MS (APCI) m/z 409 [M+H]+

Workup

  1. customA 15-mL, round bottomed flask equipped with a magnetic stirrer
  2. customwas purged with nitrogen
  3. concentrationthe reaction was concentrated under reduced pressure
  4. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-48a3bd44f2f84db4bda3a2ada1f88ea8
Source dataset
uspto-grants-2010_08
Patent number
US07781430B2

Reaction notes

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