Morpholine → 2-(3-{3-[(2-Chloro-3-(trifluoromethyl)-benzyl)-(2,2-diphenylethyl)-amino]-propoxy}phenyl)-1-morpholinyl-ethanone hydrochloride salt

HRID 1296962ノート

反応式

HRID 1296962 の反応式
[Cl:1][C:2]1[C:37]([C:38]([F:41])([F:40])[F:39])=[CH:36][CH:35]=[CH:34][C:3]=1[CH2:4][N:5]([CH2:20][CH:21]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH2:6][CH2:7][CH2:8][O:9][C:10]1[CH:11]=[C:12]([CH2:16][C:17]([OH:19])=O)[CH:13]=[CH:14][CH:15]=1.[NH:42]1[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC>CC#N>[ClH:1].[Cl:1][C:2]1[C:37]([C:38]([F:39])([F:40])[F:41])=[CH:36][CH:35]=[CH:34][C:3]=1[CH2:4][N:5]([CH2:20][CH:21]([C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:6][CH2:7][CH2:8][O:9][C:10]1[CH:11]=[C:12]([CH2:16][C:17]([N:42]2[CH2:47][CH2:46][O:45][CH2:44][CH2:43]2)=[O:19])[CH:13]=[CH:14][CH:15]=1

参加物

6

反応物 4

HCID 8083MorpholineHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 4479053-(3-(((2-Chloro-3-(trifluoromethyl)phenyl)methyl)(2,2-diphenylethyl)amino)propoxy)benzeneacetic acid

生成物 1

HCID 117651892-(3-{3-[(2-Chloro-3-(trifluoromethyl)-benzyl)-(2,2-diphenylethyl)-amino]-propoxy}phenyl)-1-morpholinyl-ethanone hydrochloride salt収率 108.2%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

2-(3-{3-[[2-chloro-3-(trifluoromethyl)benzyl)(2,2-diphenylethyl)-amino]-propoxy}-phenyl acetic acid (50 mg, 0.086 mmole) and morpholine (8.7 mg, 0.10 mmole) were dissolved in CH3CN (2 ml). BOP reagent (44 mg, 0.10 mmole) was added followed by Et3N (20 mg, 0.20 mmole). The resultant mixture was stirred at room temperature for 2 h. The mixture was concentrated under reduced pressure. The residue was partitioned between EtOAc and aqueous Na2CO3 (5%) solution. The organic layer was separated, dried over MgSO4 and concentrated. In cases where the product required further purification, a preparative Gilson HPLC was used (YMC CombiPrep ODS-A, 50×20 mm, 20 ml/min, 30–90% CH3CN over 15 minutes). The HCl salt was made by adding HCl (in ether) to an ether solution of the product and then evaporation of the solvent to give a yellow solid (32 mg, 54%). MS(ES) m/e 651.2 [M+H]+.

後処理

  1. concentrationThe mixture was concentrated under reduced pressure
  2. customThe residue was partitioned between EtOAc and aqueous Na2CO3 (5%) solution
  3. customThe organic layer was separated
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customIn cases where the product required further purification
  7. custom(YMC CombiPrep ODS-A, 50×20 mm, 20 ml/min, 30–90% CH3CN over 15 minutes)
  8. additionby adding HCl (in ether) to an ether solution of the product
  9. customevaporation of the solvent

出典と根拠

ORDレコード
ord-164752eb7b924d36a2149aa7bfefe7f9
出典データセット
uspto-grants-2007_07
特許番号
US07247748B2

反応ノート

読み込み中…