1-Hydroxybenzotriazole → HCID 68412936, compound

HRID 220297Notes

Reaction equation

HRID 220297 reaction equation
[OH:1][C:2]1([CH2:15][C:16](O)=[O:17])[CH2:7][CH:6]2[CH2:8][CH2:9][CH:3]1[CH:4]=[C:5]2[C:10]1[S:11][CH:12]=[CH:13][CH:14]=1.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.[NH:38]1[C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][C:41]=2[N:40]=[C:39]1[CH2:47][CH2:48][CH2:49][NH:50][CH3:51]>C1COCC1.C(Cl)Cl.C(Cl)CCl>[NH:38]1[C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][C:41]=2[N:40]=[C:39]1[CH2:47][CH2:48][CH2:49][N:50]([CH3:51])[C:16](=[O:17])[CH2:15][C:2]1([OH:1])[CH2:7][CH:6]2[CH2:8][CH2:9][CH:3]1[CH:4]=[C:5]2[C:10]1[S:11][CH:12]=[CH:13][CH:14]=1

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 31454002-(3-(methylamino)propyl)-1H-benzimidazoleHCID 68412916HCID 68412916, compound

Product 1

HCID 68412936HCID 68412936, compoundYield 49.8%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

100 mg of rac-(1R*,2R*,4R*)-(2-hydroxy-5-thiophen-2-yl-bicyclo[2.2.2]oct-5-en-2-yl)-acetic acid were dissolved in THF (0.15 mL)/DCM (0.6 mL). 0.194 mL of DIPEA, 77 mg of HOBt and 109 mg of EDC were added sequentially at rt. The reaction mixture was stirred for 10 min then 86 mg of [3-(1H-benzoimidazol-2-yl)-propyl]-methyl-amine were added at rt. The reaction mixture was stirred on at rt then diluted with DCM and washed with sat.-NaHCO3 and brine. The organic phase was dried over anh. Na2SO4, filtered and concentrated in vacuo. The resulting crude material was purified by CC using EtOAc/MeOH/NEt3 as eluant from 98/2/1 to 70/30/1 to yield 82 mg of rac-(1R*,2R*,4R*)-N-[3-(1H-benzoimidazol-2-yl)-propyl]-2-(2-hydroxy-5-thiophen-2-yl-bicyclo[2.2.2]oct-5-en-2-yl)-N-methyl-acetamide as a colorless oil.

Workup

  1. stirringThe reaction mixture was stirred on at rt
  2. washwashed with sat.-NaHCO3 and brine
  3. dry with materialThe organic phase was dried over anh. Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resulting crude material was purified by CC

Sources & evidence

ORD record
ord-92e3db3700f44a2eb8769b957e69010a
Source dataset
uspto-grants-2012_06
Patent number
US08202885B2

Reaction notes

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