Triethylamine → 4-Cyano-N,N,5-trimethyl-7-[(3S)-3-(methylamino)pyrrolidin-1-yl]-6-(thiophen-2-yl)-1,3-benzoxazole-2-carboxamide

HRID 17598Notes

Reaction equation

HRID 17598 reaction equation
[C:1]([C:3]1[C:8]2[N:9]=[C:10]([C:12]([N:14]([CH3:16])[CH3:15])=[O:13])[O:11][C:7]=2[C:6](F)=[C:5]([C:18]2[S:19][CH:20]=[CH:21][CH:22]=2)[C:4]=1[CH3:23])#[N:2].C(N(CC)CC)C.[CH3:31][NH:32][C@H:33]1[CH2:37][CH2:36][NH:35][CH2:34]1>CS(C)=O>[C:1]([C:3]1[C:8]2[N:9]=[C:10]([C:12]([N:14]([CH3:16])[CH3:15])=[O:13])[O:11][C:7]=2[C:6]([N:35]2[CH2:36][CH2:37][C@H:33]([NH:32][CH3:31])[CH2:34]2)=[C:5]([C:18]2[S:19][CH:20]=[CH:21][CH:22]=2)[C:4]=1[CH3:23])#[N:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10261057(3S)-(-)-3-(Methylamino)pyrrolidineHCID 685859004-Cyano-7-fluoro-N,N,5-trimethyl-6-(thiophen-2-yl)-1,3-benzoxazole-2-carboxamide

Product 1

HCID 685849524-Cyano-N,N,5-trimethyl-7-[(3S)-3-(methylamino)pyrrolidin-1-yl]-6-(thiophen-2-yl)-1,3-benzoxazole-2-carboxamideYield 60%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

4-Cyano-7-fluoro-N,N,5-trimethyl-6-(thiophen-2-yl)-1,3-benzoxazole-2-carboxamide (I-308) (160 mg, 0.49 mmol) was dissolved in dimethyl sulfoxide (8.7 ml), and at room temperature, triethylamine (81 μl, 0.58 mmol) was added. The solution was gradually heated from room temperature up to 150° C., and a solution of (3S)-3-(methylamino)pyrrolidine (62 μl, 0.58 mmol) dissolved in dimethyl sulfoxide (1 ml) was added all at a time. After stirred at the same temperature for 50 minutes, this was cooled to room temperature. The solvent was evaporated away under reduced pressure, and the resulting residue was fractionated with chloroform and saturated brine. The aqueous layer was further fractionated twice with chloroform. The organic layers were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The insoluble matter was separated by filtration, the solvent was evaporated away, and the resulting residue was roughly purified by preparative TLC (eluent, chloroform:7 N ammonia/methanol solution=95:5, v/v), and the roughly-purified product was again purified by preparative TLC (eluent, chloroform:methanol=9:1, v/v) to obtain the entitled compound (119 mg, 60%) as a yellow amorphous substance.

Workup

  1. temperatureThe solution was gradually heated from room temperature up to 150° C.
  2. additionwas added all at a time
  3. customThe solvent was evaporated away under reduced pressure
  4. washwashed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe insoluble matter was separated by filtration
  7. customthe solvent was evaporated away
  8. customthe resulting residue was roughly purified by preparative TLC (eluent, chloroform
  9. custom7 N ammonia/methanol solution=95:5, v/v), and the roughly-purified product was again purified by preparative TLC (eluent, chloroform

Sources & evidence

ORD record
ord-25127ffa1b6142e2b5d7726150419488
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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