Dimethylamine → (S)-2-(Dimethylamino)-N-(3-hydroxy-5-(4-((1-(5-methyl-4-oxo-3-phenyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl)amino)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)phenyl)ethanesulfonamide

HRID 1052548노트

반응식

HRID 1052548 반응식
[NH2:1][C:2]1[CH:3]=[C:4]([C:9]2[C:17]3[C:16]([NH:18][C@H:19]([C:21]4[N:26]([C:27]5[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=5)[C:25](=[O:33])[C:24]5=[C:34]([CH3:37])[CH:35]=[CH:36][N:23]5[N:22]=4)[CH3:20])=[N:15][CH:14]=[N:13][C:12]=3[N:11]([CH2:38][O:39][CH2:40][CH2:41][Si:42]([CH3:45])([CH3:44])[CH3:43])[CH:10]=2)[CH:5]=[C:6]([OH:8])[CH:7]=1.[CH2:46]([N:48]([CH2:51]C)[CH2:49]C)[CH3:47].ClCC[S:56](Cl)(=[O:58])=[O:57].CNC>O1CCCC1.O>[CH3:49][N:48]([CH3:51])[CH2:46][CH2:47][S:56]([NH:1][C:2]1[CH:3]=[C:4]([C:9]2[C:17]3[C:16]([NH:18][C@H:19]([C:21]4[N:26]([C:27]5[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=5)[C:25](=[O:33])[C:24]5=[C:34]([CH3:37])[CH:35]=[CH:36][N:23]5[N:22]=4)[CH3:20])=[N:15][CH:14]=[N:13][C:12]=3[N:11]([CH2:38][O:39][CH2:40][CH2:41][Si:42]([CH3:43])([CH3:45])[CH3:44])[CH:10]=2)[CH:5]=[C:6]([OH:8])[CH:7]=1)(=[O:58])=[O:57]

참가 물질

7

반응물 4

HCID 674DimethylamineHCID 8471TriethylamineHCID 15385Ethanesulfonylchloride, 2-chloro-HCID 90103036(S)-2-(1-((5-(3-Amino-5-hydroxyphenyl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one

생성물 1

HCID 131736196(S)-2-(Dimethylamino)-N-(3-hydroxy-5-(4-((1-(5-methyl-4-oxo-3-phenyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl)amino)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)phenyl)ethanesulfonamide수율 13%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매2회

실험 절차

(S)-2-(1-((5-(3-Amino-5-hydroxyphenyl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (75 mg, 0.12 mmol) was dissolved in 3.75 ml tetrahydrofuran. Triethylamine (50 μl, 0.36 mmol) and 2-chloroethanesulfonyl chloride (15 μL, 0.14 mmol) were added and the mixture was stirred at room temperature during 2 h. Dimethylamine 2M in tetrahydrofuran (301 μl, 0.60 mmol) was added and the mixture was stirred again at room temperature during 4 h. The reaction was poured into water and extracted twice with ethyl acetate. The organics were combined and washed with water, brine, dried over sodium sulphate, filtered and evaporated under reduced pressure. The residue was purified using SP1® Purification System (0% to 30% dichloromethane-2-propanol) to obtain 15 mg (13% yield, 77% purity) of the title compound.

후처리

  1. stirringthe mixture was stirred again at room temperature during 4 h
  2. extractionextracted twice with ethyl acetate
  3. washwashed with water, brine
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customThe residue was purified
  8. customSP1® Purification System (0% to 30% dichloromethane-2-propanol)

출처 및 근거

ORD 기록
ord-8c6111a220f5467794593640c5ec47d6
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09388189B2

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