Dimethyl Sulfoxide → Ammonium Hydroxide

HRID 2294933Notes

Reaction equation

HRID 2294933 reaction equation
C(Cl)(=O)C(Cl)=[O:3].CS(C)=O.[N:11]1[CH:16]=[C:15]([CH:17]([OH:40])[C@@H:18]2[CH2:23][CH2:22][C@H:21]([N:24]3[CH2:29][CH2:28][CH:27]([N:30]4[C:34]5[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=5[NH:32][C:31]4=[O:39])[CH2:26][CH2:25]3)[CH2:20][CH2:19]2)[CH:14]=[N:13][CH:12]=1.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl.O.C(N(CC)CC)C>[NH4+:11].[OH-:3].[N:11]1[CH:16]=[C:15]([C:17]([C@H:18]2[CH2:23][CH2:22][C@H:21]([N:24]3[CH2:29][CH2:28][CH:27]([N:30]4[C:34]5[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=5[NH:32][C:31]4=[O:39])[CH2:26][CH2:25]3)[CH2:20][CH2:19]2)=[O:40])[CH:14]=[N:13][CH:12]=1

Participants

9

Reactant 4

HCID 679Dimethyl SulfoxideHCID 10340Sodium CarbonateHCID 65578Oxalyl chlorideHCID 178518593HCID 178518593, compound

Product 2

HCID 14923Ammonium HydroxideYield 1%HCID 178518594HCID 178518594, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

To a stirred solution of oxalyl chloride (68 mg) in dry dichloromethane (4 mL) at -60° C., under argon, was added dry dimethyl sulfoxide (0.107 mL) dropwise. The resulting mixture was stirred for 5 min, then added to a solution of (±)-cis-1,3-dihydro-1-(1-{4-[(5-pyrimidinyl)hydroxymethyl]cyclohex-1-yl}piperidin-4-yl)-2H -benzimidazol-2-one (112 mg) in dichloromethane (5 mL) at -60° C. The reaction mixture was stirred for 20 min at -60° C., then triethylamine (0.54 mL) was added and the solution was allowed to warm to room temperature. Water was added and the mixture stirred for a further 10 min, after which saturated sodium carbonate was added and the mixture was extracted with dichloromethane (3×20 mL). The combined extracts were dried (MgSO4) and concentrated in vacuo. Purification by preparative TLC on silica eluting with chloroform; 7% methanol; 1% NH4OH, followed by a second purification eluting with dichloromethane; 10% methanol; 1% NH4OH yielded trans-1,3-dihydro-1-{1-[4-(5-pyrimidinylcarbonyl)cyclohex-1-yl]piperidin-4-yl}-2H-benzimidazol-2-one: 1H NMR (400 MHz, CDCl3 ; CD3 OD) 9.34 (s, 1H), 9.30 (s, 2H), 7.43 (m, 1H), 7.11-7.04 (m, 3H), 4.40 (tt, 1H), 3.36 (m, 1H), 3.28 (d, 2H), 2.73-2.57 (m, 5H), 2.24-2.10 (m, 4H), 1.90 (m, 2H), 1.633 (m, 4H). m/z (FAB): 406 (MH+). The hydrochloride salt was precipitated from ethanol/chloroform: analysis calculated for C23H27N5O2.2 HCl.0.75 H2O.0.35 C2 H5OH C: 56.03, H: 6.47, N: 13.78; found C: 56.03, H: 6.14, N: 13.76.

Workup

  1. stirringThe reaction mixture was stirred for 20 min at -60° C.
  2. stirringthe mixture stirred for a further 10 min
  3. extractionthe mixture was extracted with dichloromethane (3×20 mL)
  4. dry with materialThe combined extracts were dried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customPurification by preparative TLC on silica eluting with chloroform
  7. custom1% NH4OH, followed by a second purification
  8. washeluting with dichloromethane

Sources & evidence

ORD record
ord-f22f7b655f99467dae47dc7fd6f2f428
Source dataset
uspto-grants-1997_11
Patent number
US05691323

Reaction notes

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