Diisopropylethylamine → Perk-IN-6

HRID 1910061ノート

反応式

HRID 1910061 の反応式
Cl.Cl.[NH:3]1[C:11]2[C:6](=[CH:7][C:8]([C:12]3[C:20]4[C:19]([NH2:21])=[N:18][CH:17]=[N:16][C:15]=4[N:14]([CH3:22])[CH:13]=3)=[CH:9][CH:10]=2)[CH2:5][CH2:4]1.OC(C(F)(F)F)=O.[CH3:30][C:31]1[N:36]=[C:35]([CH2:37][C:38](O)=[O:39])[CH:34]=[CH:33][CH:32]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C)C=O.O>[CH3:22][N:14]1[C:15]2[N:16]=[CH:17][N:18]=[C:19]([NH2:21])[C:20]=2[C:12]([C:8]2[CH:7]=[C:6]3[C:11](=[CH:10][CH:9]=2)[N:3]([C:38](=[O:39])[CH2:37][C:35]2[CH:34]=[CH:33][CH:32]=[C:31]([CH3:30])[N:36]=2)[CH2:4][CH2:5]3)=[CH:13]1

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 668234705-(2,3-dihydro-1H-indol-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine dihydrochlorideHCID 66823699(6-methyl-2-pyridinyl)acetic acid TFA salt

生成物 1

HCID 53468860Perk-IN-6収率 95%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

A solution of 5-(2,3-dihydro-1H-indol-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine 2HCl (150 mg, 0.443 mmol), (6-methyl-2-pyridinyl)acetic acid TFA salt (118 mg, 0.443 mmol), HATU (169 mg, 0.443 mmol), and DIEA (0.387 mL, 2.217 mmol) in N,N-Dimethylformamide (DMF) (3 mL) were stirred overnight at room temperature. At this time, LCMS analysis indicated complete conversion, so water (15 mL) was added to the reaction mixture, and the resulting mixture stirred for 30 minutes at room temperature, forming an emulsion-like mixture. The mixture was extracted with ethyl acetate: methanol (ca. 1% methanol, 3×30 mL) and the combined organics were dried over sodium sulfate, filtered and concentrated. The residue was adsorbed onto silica and purified by flash chromatography (0-10% MeOH in EtOAc, 12-g column) to afford 7-methyl-5-{1-[(6-methyl-2-pyridinyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7H-pyrrolo[2,3-d]pyrimidin-4-amine (167.3 mg, 0.420 mmol, 95% yield) as an off-white solid. LC-MS (ES) m/z=399 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.46 (s, 3H), 3.23 (t, J=8.34 Hz, 2H), 3.75 (s, 3H), 4.00 (s, 2H), 4.29 (t, J=8.46 Hz, 2H), 6.01-6.41 (m, 2H), 7.17 (t, J=7.33 Hz, 2H), 7.23 (d, J=8.34 Hz, 1H), 7.27-7.34 (m, 2H), 7.68 (t, J=7.58 Hz, 1H), 8.12 (d, J=8.08 Hz, 1H), 8.18 (s, 1H).

後処理

  1. additionwas added to the reaction mixture
  2. customforming an emulsion-like mixture
  3. extractionThe mixture was extracted with ethyl acetate
  4. dry with materialmethanol (ca. 1% methanol, 3×30 mL) and the combined organics were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by flash chromatography (0-10% MeOH in EtOAc, 12-g column)

出典と根拠

ORDレコード
ord-1e53cc3401c74403b1f914ec97c115bf
出典データセット
uspto-grants-2013_12
特許番号
US08598156B2

反応ノート

読み込み中…