Methylamine → HCID 178485537, 화합물

HRID 1014479노트

반응식

HRID 1014479 반응식
Cl.Cl[C:3]1[N:16]2[C:7](=[N:8][C:9]3[C:14]([C:15]2=[O:17])=[C:13]([F:18])[CH:12]=[CH:11][CH:10]=3)[C:6]2[CH:19]=[CH:20][N:21](S(C3C=CC(C)=CC=3)(=O)=O)[C:5]=2[N:4]=1.[CH3:32][O:33][C:34]1[CH:35]=[C:36]2[C:40](=[CH:41][C:42]=1[NH2:43])[N:39]([C:44](=[O:48])[CH2:45][O:46][CH3:47])[CH2:38][CH2:37]2.[CH3:49][NH2:50].[OH-].[K+].[OH-].[Na+]>C1COCC1.CCOC(C)=O>[F:18][C:13]1[CH:12]=[CH:11][CH:10]=[C:9]([NH:8][C:7]2[N:16]=[C:3]([NH:43][C:42]3[CH:41]=[C:40]4[C:36]([CH2:37][CH2:38][N:39]4[C:44](=[O:48])[CH2:45][O:46][CH3:47])=[CH:35][C:34]=3[O:33][CH3:32])[NH:4][C:5]3=[N:21][CH:20]=[CH:19][C:6]=23)[C:14]=1[C:15]([NH:50][CH3:49])=[O:17]

참가 물질

8

반응물 5

HCID 6329MethylamineHCID 14797Potassium HydroxideHCID 14798Sodium HydroxideHCID 594417515-(methyloxy)-1-[(methyloxy)acetyl]-2,3-dihydro-1H-indol-6-amineHCID 673162535-chloro-8-fluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2',3':4,5]pyrimido[6,1-b]quinazolin-7(3H)-one HCl salt

생성물 1

HCID 178485537HCID 178485537, 화합물수율 26.7%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

A thick white slurry of 5-chloro-8-fluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one hydrogen chloride (400 mg, 0.835 mmol) and 5-(methyloxy)-1-[(methyloxy)acetyl]-2,3-dihydro-1H-indol-6-amine (197 mg, 0.835 mmol) in THF (15 mL) was heated at 80° C. After 17 h a methylamine solution (2 N in THF, 4.17 mL, 8.35 mmol) was added. The reaction mixture was maintained at rt for 22 h, then filtered, the solid washed with THF. The filtrate was concentrated onto Celite and purified by silica gel chromatography using 1-10% MeOH (containing 0.2% NH3)/CH2Cl2. The crude product was dissolved in dioxane (15 mL) and a 1N KOH solution (4.38 mL, 4.38 mmol), then heated at 80° C. After 3 h the reaction mixture was allowed to cool somewhat, diluted with EtOAc (100 mL) and a 2N NaOH solution (50 mL). The organic layer was washed with a 2N NaOH solution (2×50 mL), concentrated onto Celite and purified by silica gel chromatography using 1-10% MeOH (containing 0.2% NH3)/CH2Cl2 to obtain 2-fluoro-N-methyl-6-{[2-({5-(methyloxy)-1-[(methyloxy)acetyl]-2,3-dihydro-1H-indol-6-yl}amino)-1H-pyrrolo[2,3-d]pyrimidin-4-yl]amino}benzamide as a yellow solid (116 mg). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.80 (d, J=4.39 Hz, 3H), 3.13 (t, J=8.24 Hz, 2H), 3.79 (s, 3H), 4.04 (t, J=8.24 Hz, 2H), 4.17 (s, 2H), 6.25-6.34 (m, 1H), 6.84-7.04 (m, 3H), 7.27-7.40 (m, 1H), 7.58 (s, 1H), 8.35 (d, J=8.24 Hz, 1H), 8.50-8.61 (m, 1H), 8.68 (s, 1H), 10.16 (s, 1H), 11.30 (s, 1H), a Me-O signal with 3 protons is missing, may overlap with water peak in sample; ESIMS (M+H)+=520.16.

후처리

  1. filtrationfiltered
  2. washthe solid washed with THF
  3. concentrationThe filtrate was concentrated onto Celite
  4. custompurified by silica gel chromatography
  5. dissolutionThe crude product was dissolved in dioxane (15 mL)
  6. temperatureto cool somewhat
  7. washThe organic layer was washed with a 2N NaOH solution (2×50 mL)
  8. concentrationconcentrated onto Celite
  9. custompurified by silica gel chromatography

출처 및 근거

ORD 기록
ord-19a65f1ababd48c191e45c09934fc921
출처 데이터셋
uspto-grants-2011_07
특허 번호
US07981903B2

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