Triethylamine → Methyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclopentylamino)-4-cyano-2-(3-(methylsulfonyl)phenylamino)nicotinate

HRID 711482ノート

反応式

HRID 711482 の反応式
Cl[C:2]1[CH:11]=[C:10]([C:12]#[N:13])[C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([S:21]([CH3:24])(=[O:23])=[O:22])[CH:16]=2)[N:3]=1.CCN(CC)CC.[NH2:32][C@@H:33]1[CH2:37][CH2:36][CH2:35][C@@H:34]1[NH:38][C:39](=[O:45])[O:40][C:41]([CH3:44])([CH3:43])[CH3:42].C([O-])(O)=O.[Na+]>CN(C=O)C>[C:41]([O:40][C:39]([NH:38][C@H:34]1[CH2:35][CH2:36][CH2:37][C@H:33]1[NH:32][C:2]1[CH:11]=[C:10]([C:12]#[N:13])[C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([S:21]([CH3:24])(=[O:23])=[O:22])[CH:16]=2)[N:3]=1)=[O:45])([CH3:44])([CH3:42])[CH3:43]

参加物

6

反応物 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 45091940tert-butyl N-[(1S,2R)-2-aminocyclopentyl]carbamateHCID 58317716Methyl 6-chloro-4-cyano-2-(3-(methylsulfonyl)phenylamino)nicotinate

生成物 1

HCID 67238760Methyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclopentylamino)-4-cyano-2-(3-(methylsulfonyl)phenylamino)nicotinate収率 61.5%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
60 °C

実験手順

A mixture of methyl 6-chloro-4-cyano-2-(3-(methylsulfonyl)phenylamino)nicotinate (165.0 mg, 0.451 mmol), Et3N (0.15 mL, 1.076 mmol), and tert-butyl (1S,2R)-2-aminocyclopentylcarbamate (142.0 mg, 0.709 mmol) in DMF (6 mL) was stirred at 60° C. for 12 h. Saturated aq NaHCO3 (20 mL) was added to the mixture, which was subsequently extracted with EtOAc (2×30 mL). The organic layers were washed with saturated aq NaHCO3 (20 mL), water (20 mL) and brine (20 mL), were dried over anhydrous Na2SO4, and filtered (DM1020). The filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (SiO2, hexanes/EtOAc=1/1) and then triturated with IPE to provide the title compound (147 mg).

後処理

  1. extractionwas subsequently extracted with EtOAc (2×30 mL)
  2. washThe organic layers were washed with saturated aq NaHCO3 (20 mL), water (20 mL) and brine (20 mL)
  3. dry with materialwere dried over anhydrous Na2SO4
  4. filtrationfiltered (DM1020)
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customThe residue was purified by column chromatography (SiO2, hexanes/EtOAc=1/1)
  7. customtriturated with IPE

出典と根拠

ORDレコード
ord-46d411fb2dd94e149f5aa7ddbb23ee7e
出典データセット
uspto-grants-2015_11
特許番号
US09181255B2

反応ノート

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