Triethylamine → methyl 4-cyano-2-cyclopropyl-7-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-5-methyl-1,3-benzoxazole-6-carboxylate

HRID 17465노트

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HRID 17465 반응식
[C:1]([C:3]1[C:8]2[N:9]=[C:10]([CH:12]3[CH2:14][CH2:13]3)[O:11][C:7]=2[C:6](F)=[C:5]([C:16]([O:18][CH3:19])=[O:17])[C:4]=1[CH3:20])#[N:2].C(N(CC)CC)C.[CH3:28][N:29]([CH3:35])[C@H:30]1[CH2:34][CH2:33][NH:32][CH2:31]1.C(=O)([O-])O.[Na+]>C(OCC)(=O)C>[C:1]([C:3]1[C:8]2[N:9]=[C:10]([CH:12]3[CH2:14][CH2:13]3)[O:11][C:7]=2[C:6]([N:32]2[CH2:33][CH2:34][C@H:30]([N:29]([CH3:35])[CH3:28])[CH2:31]2)=[C:5]([C:16]([O:18][CH3:19])=[O:17])[C:4]=1[CH3:20])#[N:2]

참가 물질

6

반응물 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 7019156(3S)-(-)-3-(Dimethylamino)pyrrolidineHCID 68584578Methyl 4-cyano-2-cyclopropyl-7-fluoro-5-methyl-1,3-benzoxazole-6-carboxylate

생성물 1

HCID 68585780methyl 4-cyano-2-cyclopropyl-7-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-5-methyl-1,3-benzoxazole-6-carboxylate수율 86.6%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

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온도
90 °C

실험 절차

Methyl 4-cyano-2-cyclopropyl-7-fluoro-5-methyl-1,3-benzoxazole-6-carboxylate (I-183) (100 mg, 0.37 mmol) was dissolved in dimethyl, then at room temperature, triethylamine (76 μl, 0.55 mmol) and (3S)-3-(dimethylamino)pyrrolidine (56 μl, 0.44 mmol) were added. The solution was stirred under nitrogen atmosphere at 90° C. for 10 hours, then cooled to room temperature. This was fractionated with ethyl acetate and an aqueous saturated sodium hydrogencarbonate solution. The aqueous layer was further extracted twice with ethyl acetate. The organic layers were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The insoluble matter was separated by filtration, then the solvent was evaporated away, and the resulting residue was purified by preparative TLC (eluent, chloroform:methanol=92:8) to obtain the entitled compound (118 mg) as a roughly-purified product. This was washed with diisopropyl ether to obtain the entitled compound (109 mg, 81%) as a white solid.

후처리

  1. temperaturecooled to room temperature
  2. extractionThe aqueous layer was further extracted twice with ethyl acetate
  3. washwashed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe insoluble matter was separated by filtration
  6. customthe solvent was evaporated away
  7. customthe resulting residue was purified by preparative TLC (eluent, chloroform:methanol=92:8)

출처 및 근거

ORD 기록
ord-a8a243d9cc694ed2a7e1384c5463c0a4
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07737166B2

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