Trifluoroacetic acid → HCID 57418648、化合物

HRID 2354399ノート

反応式

HRID 2354399 の反応式
[C:1]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:6]=[CH:5][C:4]([CH:7]([NH:14][CH3:15])[CH2:8][N:9]2[CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:3][CH:2]=1.[CH3:22][O:23][C:24]1[C:38]([C:39]([F:42])([F:41])[F:40])=[CH:37][C:27]2[N:28]([CH2:33][C:34]([OH:36])=O)[C:29](=[O:32])[CH2:30][O:31][C:26]=2[CH:25]=1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.FC(F)(F)C(O)=O>CN(C)C=O.CC#N.O>[C:1]1([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:6]=[CH:5][C:4]([CH:7]([N:14]([CH3:15])[C:34](=[O:36])[CH2:33][N:28]2[C:27]3[CH:37]=[C:38]([C:39]([F:42])([F:41])[F:40])[C:24]([O:23][CH3:22])=[CH:25][C:26]=3[O:31][CH2:30][C:29]2=[O:32])[CH2:8][N:9]2[CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:3][CH:2]=1

参加物

8

反応物 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 27567161-([1,1'-Biphenyl]-4-yl)-N-methyl-2-(pyrrolidin-1-yl)ethan-1-amineHCID 57457166HCID 57457166、化合物

生成物 1

HCID 57418648HCID 57418648、化合物収率 41%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒2 回HCID 18373917Acetonitrile--water (1/1)溶媒

実験手順

[1-(4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]methylamine (0.084 g, 0.30 mmol) and [7-(methyloxy)-3-oxo-6-(trifluoromethyl)-2,3-dihydro-4H-1,4-benzoxazin-4-yl]acetic acid (0.1 g, 0.33 mmol) were dissolved in 1 mL of dimethylformamide. Triethylamine (0.13 mL, 0.9 mmol) was delivered to the room temperature mixture, and the solution was allowed to stir for several minutes before a separate solution of 1H-1,2,3-benzotriazol-1-yloxy-tris(dimethylamino)-phosphonium hexafluorophosphate (BOP reagent, 0.146 g, 0.33 mmol) dissolved in 1 mL of dimethylformamide was added to the mixture at room temperature. The reaction was maintained at that temperature for 18 hours, before it was determined to be complete by LCMS (two Aquasil C18, 20×1 mm columns were run in sequence, 4 minutes at 0.1 mL/min, 1-99% CH3CN/H2O with 0.018% trifluoroacetic acid, ES) Rt=2.1 min and m/e 568 [M+1]+. The reaction mixture was filtered through a 0.45 μm PTFE Acrodisk and the crude residue was purified by prep HPLC (Waters, 50×100 mm, 84 mL/min, A: acetonitrile B: water (pH=10, NH4OH), A: 10 to 99% over 15 min, UV detection at 214 nm) to give the title compound (0.070 g. 0.12 mmol, 41%) as an off-white amorphous solid. MS (ES) m/e 568 [M+H]+.

後処理

  1. customwas delivered to the room temperature mixture
  2. additionwas added to the mixture at room temperature
  3. temperatureThe reaction was maintained at that temperature for 18 hours, before it
  4. filtrationThe reaction mixture was filtered through a 0.45 μm PTFE Acrodisk
  5. customthe crude residue was purified by prep HPLC (Waters, 50×100 mm, 84 mL/min

出典と根拠

ORDレコード
ord-f8ead9528b81416f9f16592ebbd93aea
出典データセット
uspto-grants-2010_07
特許番号
US07749998B2

反応ノート

読み込み中…