Methanol → HCID 18735040, compound

HRID 844489Notes

Reaction equation

HRID 844489 reaction equation
[ClH:1].Cl.[O:3]=[C:4]1[N:8]([CH:9]2[CH2:14][CH2:13][N:12]([CH2:15][C:16]([NH:18][C@H:19]3[CH2:28][CH2:27][C:26]4[C:21](=[CH:22][CH:23]=[C:24]([O:29]C)[CH:25]=4)[C@H:20]3[CH2:31][C:32]3[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=3)=[O:17])[CH2:11][CH2:10]2)[C:7]2[CH:38]=[CH:39][CH:40]=[CH:41][C:6]=2[NH:5]1.B(Br)(Br)Br.CO>ClCCl>[ClH:1].[ClH:1].[O:3]=[C:4]1[N:8]([CH:9]2[CH2:10][CH2:11][N:12]([CH2:15][C:16]([NH:18][C@H:19]3[CH2:28][CH2:27][C:26]4[C:21](=[CH:22][CH:23]=[C:24]([OH:29])[CH:25]=4)[C@H:20]3[CH2:31][C:32]3[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=3)=[O:17])[CH2:13][CH2:14]2)[C:7]2[CH:38]=[CH:39][CH:40]=[CH:41][C:6]=2[NH:5]1

Participants

5

Reactant 3

HCID 887MethanolHCID 25134Boron tribromideHCID 18735042HCID 18735042, compound

Product 1

HCID 18735040HCID 18735040, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 4-(2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)-N-[cis-1,2,3,4-tetrahydro-6-methoxy-1-(3-pyridinylmethyl)-2-naphthalenyl]-1-piperidineacetamide 19 (0.28 g, 0.37 mmol) in dichloromethane (2 mL) was added dropwise to a solution of boron tribromide (1.8 mmol) in dichloromethane (22 mL) at 0° C. After stirring the resultant solution at 0° C. for 1.5 h, methanol (˜2 mL) was added and stirring was continued at 0° C. for an additional 0.5 h. The solvent was evaporated in vacuo, and the residue was purified by reverse phase C18 HPLC using a water/acetonitrile/TFA gradient, 90/10/0.1 to 10/90/0.1, as the eluant. The product was dissolved in methanol and treated with ethanolic hydrochloric acid. The solvent was evaporated and the process repeated twice to give 4-(2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)-N-[cis-1,2,3,4-tetrahydro-6-hydroxy-1-(3-pyridinylmethyl)-2-naphthalenyl]-1-piperidineacetamide bis-hydrochloride salt 23 (0.148, 68%) as a colorless solid: 1H NMR(DMSO-d6) δ 1.73-2.03 (m, 4 H), 2.70-2.94 (m, 4 H), 3.05-3.20 (br s, 2 H), 3.27-3.47 (m, 3 H), 3.55-3.76 (m, 2 H), 3.92-4.15 (m, 3 H), 4.54-4.67 (m, 1H), 6.46 (d, 1H), 6.58 (s, 2 H), 7.05 (m, s, 3 H), 7.60 (br s, 1 H), 7.94 (t, 1 H), 8.30 (d, 1 H), 8.72-8.83 (m, 2 H), 8.96 (d, 1 H), 9.30 (br s, 1 H), 10.64 (br s, 1 H), and 11.05 (s, 1 H); MS m/e 512 (MH+) (Scheme 36).

Workup

  1. customThe solvent was evaporated in vacuo
  2. customthe residue was purified by reverse phase C18 HPLC
  3. dissolutionThe product was dissolved in methanol
  4. additiontreated with ethanolic hydrochloric acid
  5. customThe solvent was evaporated

Sources & evidence

ORD record
ord-b2d38a6ea0c049d09a7eb927891d0e16
Source dataset
uspto-grants-2002_04
Patent number
US06380224B1

Reaction notes

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