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

HRID 17465ノート

反応式

HRID 17465 の反応式
[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]

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

反応条件

温度
90 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-a8a243d9cc694ed2a7e1384c5463c0a4
出典データセット
uspto-grants-2010_06
特許番号
US07737166B2

反応ノート

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