Diisopropylethylamine → Perk-IN-6

HRID 1910061노트

반응식

HRID 1910061 반응식
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

참가 물질

7

반응물 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

생성물 1

HCID 53468860Perk-IN-6수율 95%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-1e53cc3401c74403b1f914ec97c115bf
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08598156B2

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