Ammonia → 4-Cyano-3-(4-methoxyphenyl)-5-morpholin-4-ylthiophene-2-carboxamide

HRID 572608ノート

反応式

HRID 572608 の反応式
[C:1]([C:3]1[C:4]([C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)=[C:5]([C:14]([OH:16])=O)[S:6][C:7]=1[N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)#[N:2].C1C=CC2N(O)N=[N:31]C=2C=1.CCN=C=NCCCN(C)C.N>C(Cl)Cl>[C:1]([C:3]1[C:4]([C:17]2[CH:18]=[CH:19][C:20]([O:23][CH3:24])=[CH:21][CH:22]=2)=[C:5]([C:14]([NH2:31])=[O:16])[S:6][C:7]=1[N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)#[N:2]

参加物

6

反応物 4

HCID 222AmmoniaHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 441558974-Cyano-3-(4-methoxyphenyl)-5-morpholin-4-ylthiophene-2-carboxylic acid

生成物 1

HCID 441557744-Cyano-3-(4-methoxyphenyl)-5-morpholin-4-ylthiophene-2-carboxamide収率 81.5%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

4-Cyano-3-(4-methoxyphenyl)-5-morpholin-4-ylthiophene-2-carboxylic acid (0.035 g, 0.10 mmol), HOBT (0.028 g, 0.18 mmol) and EDCI (38 mg, 0.20 mmol) were suspended in DCM (5 mL). After 50 min the reagents dissolved. To the resulting solution was added concentrated aqueous ammonia (0.2 mL, 5 mmol) and the solution was allowed to stir vigorously at rt for 2 h. The reaction mixture was concentrated and the residue was diluted with 1N HCl and extracted with EtOAc. The organic solutions were combined, washed with sat NaHCO3 and brine, dried over MgSO4 filtered and concentrated to give 4-cyano-3-(4-methoxyphenyl)-5-morpholin-4-ylthiophene-2-carboxamide (66) (0.028 g, 80%). LCMS: (AA) ES+ 344. 1H NMR (400 MHz, d6-DMSO) δ: 7.32-7.35 (m, 2H), 7.06-7.09 (m, 2H), 3.82 (s, 3H), 3.76-3.78 (m, 4H) and 3.52-3.54 (m, 4H).

後処理

  1. dissolutionAfter 50 min the reagents dissolved
  2. concentrationThe reaction mixture was concentrated
  3. additionthe residue was diluted with 1N HCl
  4. extractionextracted with EtOAc
  5. washwashed with sat NaHCO3 and brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated

出典と根拠

ORDレコード
ord-b336dc46c97547f6ba95714aceccc052
出典データセット
uspto-grants-2015_05
特許番号
US09029411B2

反応ノート

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