3-(Trifluoromethyl)benzeneacetic acid → 3-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)thieno[3,2-c]pyridin-4-amine

HRID 1909943ノート

反応式

HRID 1909943 の反応式
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]3[C:14]4[C:15]([NH2:19])=[N:16][CH:17]=[CH:18][C:13]=4[S:12][CH:11]=3)=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:44][C:45]([F:57])([F:56])[C:46]1[CH:47]=[C:48]([CH2:52][C:53](O)=[O:54])[CH:49]=[CH:50][CH:51]=1.CCN(C(C)C)C(C)C>O.CN(C)C=O>[F:44][C:45]([F:56])([F:57])[C:46]1[CH:47]=[C:48]([CH2:52][C:53]([N:1]2[C:9]3[C:4](=[CH:5][C:6]([C:10]4[C:14]5[C:15]([NH2:19])=[N:16][CH:17]=[CH:18][C:13]=5[S:12][CH:11]=4)=[CH:7][CH:8]=3)[CH2:3][CH2:2]2)=[O:54])[CH:49]=[CH:50][CH:51]=1

参加物

7

反応物 4

HCID 676953-(Trifluoromethyl)benzeneacetic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 668235693-(2,3-dihydro-1H-indol-5-yl)thieno[3,2-c]pyridin-4-amine

生成物 1

HCID 534696313-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)thieno[3,2-c]pyridin-4-amine収率 62.6%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a 4 mL screw cap vial was added 3-(2,3-dihydro-1H-indol-5-yl)thieno[3,2-c]pyridin-4-amine (100 mg, 0.374 mmol) followed by HATU (142 mg, 0.374 mmol), 3-trifluoromethylphenyl acetic acid (76 mg, 0.374 mmol) and DIEA (0.261 mL, 1.496 mmol). N,N-Dimethylformamide (DMF) (2 mL) was added and the reaction was sealed and left to stir at room temperature overnight. The reaction mixture was poured into water (4 mL) and extracted with EtOAc (5 mL). The organics were dried over Na2SO4 and concentrated. The residue was taken up in DCM and purified via normal phase chromatography (0-10% MeOH/DCM). Fractions were collected and concentrated to afford 3-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)thieno[3,2-c]pyridin-4-amine (106.1 mg) as an orange solid. LC/MS (ES) m/z=454.2 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.15 (d, J=8.3 Hz, 1H) 7.84 (d, J=6.1 Hz, 1H) 7.69 (s, 1H) 7.57-7.67 (m, 3H) 7.52 (s, 1H) 7.36 (d, J=5.8 Hz, 2H) 7.25 (d, J=8.1 Hz, 1H) 5.79 (br. s., 2H) 4.30 (t, J=8.5 Hz, 2H) 4.05 (s, 2H) 3.27 (t, 2H).

後処理

  1. customTo a 4 mL screw cap
  2. customthe reaction was sealed
  3. waitleft
  4. extractionextracted with EtOAc (5 mL)
  5. dry with materialThe organics were dried over Na2SO4
  6. concentrationconcentrated
  7. custompurified via normal phase chromatography (0-10% MeOH/DCM)
  8. customFractions were collected
  9. concentrationconcentrated

出典と根拠

ORDレコード
ord-5680a261c54c4008aef6172f248522d7
出典データセット
uspto-grants-2013_12
特許番号
US08598156B2

反応ノート

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