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 1052548Notes

Reaction equation

HRID 1052548 reaction equation
[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]

Participants

7

Reactant 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

Product 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)ethanesulfonamideYield 13%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

(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.

Workup

  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)

Sources & evidence

ORD record
ord-8c6111a220f5467794593640c5ec47d6
Source dataset
uspto-grants-2016_07
Patent number
US09388189B2

Reaction notes

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