Triethylamine → HCID 16071132, compound

HRID 2064212Notes

Reaction equation

HRID 2064212 reaction equation
[F:1][C:2]1[C:17]([Br:18])=[CH:16][C:5]2[N:6]([CH:10]3[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]3)[C:7](=[O:9])[NH:8][C:4]=2[CH:3]=1.[O:19]1[CH2:24][CH2:23][C:22](=O)[CH2:21][CH2:20]1.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[F:1][C:2]1[C:17]([Br:18])=[CH:16][C:5]2[N:6]([CH:10]3[CH2:15][CH2:14][N:13]([CH:22]4[CH2:23][CH2:24][O:19][CH2:20][CH2:21]4)[CH2:12][CH2:11]3)[C:7](=[O:9])[NH:8][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 121599Tetrahydro-4H-pyran-4-oneHCID 5049666Sodium triacetoxyborohydrideHCID 59850215HCID 59850215, compound

Product 1

HCID 16071132HCID 16071132, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of fluoro-6-bromo-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one (D46) (50 mg, 0.16 mmol), tetrahydro-4H-pyran-4-one (112 mg, 1.12 mmol) and triethylamine (49 mg, 0.48 mmol) in dichloromethane (5 ml) under argon was added portionwise sodium triacetoxyborohydride (240 mg, 1.12 mmol). The mixture was stirred at room temperature for 24 hrs, diluted with dichloromethane (5 ml) washed with 0.5N sodium hydroxide solution, dried (MgSO4) and concentrated in approx half volume before adding to a silica gel column which was subsequently eluted with 2-20% methanol in dichloromethane to afford 5-fluoro-6-bromo-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one. The isolated product was converted to the hydrochloride salt which was obtained as a colourless solid, 34 mg, 49%. MH+=398, and 400, 1H NMR (HCl salt) (DMSO-d6) δ: 1.24 (2H, m), 1.73 (3H, m), 1.89 (2H, m), 2.03 (2H, m), 2.83 (2H, m), 3.17 (2H, m), 3.58 (2H, m), 3.76 (1H, m), 4.59 (2H, m) 7.04 (1H, d, J=8 Hz), 7.94 (1H, d, J=5 Hz), 10.89 (1H, bs) and 11.32 (1H, s).

Workup

  1. washwashed with 0.5N sodium hydroxide solution
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated in approx half volume
  4. additionbefore adding to a silica gel column which
  5. washwas subsequently eluted with 2-20% methanol in dichloromethane

Sources & evidence

ORD record
ord-c1ab66f1b4fb4279b911ef1ee06b3453
Source dataset
uspto-grants-2012_10
Patent number
US08288412B2

Reaction notes

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