Potassium Hydroxide → {2-amino-3-fluoro-5-[3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-[4-(2-diethylamino-ethyl)-piperazin-1-yl]-methanone

HRID 2234636Notes

Reaction equation

HRID 2234636 reaction equation
[NH2:1][C:2]1[C:10]([F:11])=[CH:9][C:8]([C:12]2[CH:13]=[C:14]3[C:20]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[O:27][CH3:28])=[CH:19][N:18](S(C4C=CC(C)=CC=4)(=O)=O)[C:15]3=[N:16][CH:17]=2)=[CH:7][C:3]=1[C:4](O)=[O:5].[CH2:39]([N:41]([CH2:50][CH3:51])[CH2:42][CH2:43][N:44]1[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]1)[CH3:40].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[OH-].[K+]>CN(C)C=O.C(O)(=O)C>[NH2:1][C:2]1[C:10]([F:11])=[CH:9][C:8]([C:12]2[CH:13]=[C:14]3[C:20]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[O:27][CH3:28])=[CH:19][NH:18][C:15]3=[N:16][CH:17]=2)=[CH:7][C:3]=1[C:4]([N:47]1[CH2:46][CH2:45][N:44]([CH2:43][CH2:42][N:41]([CH2:39][CH3:40])[CH2:50][CH3:51])[CH2:49][CH2:48]1)=[O:5]

Participants

7

Reactant 4

HCID 14797Potassium HydroxideHCID 2736105N,N-Diethyl-2-(piperazin-1-yl)ethan-1-amineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 577314302-amino-3-fluoro-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-benzoic acid

Product 1

HCID 59700260{2-amino-3-fluoro-5-[3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-[4-(2-diethylamino-ethyl)-piperazin-1-yl]-methanoneYield 21%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6228DimethylformamideSolvent

Procedure

24 mg (0.05 mmol) of 2-amino-3-fluoro-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-benzoic acid, 8.4 mg (0.05 mmol) of 1-(2-diethylaminoethyl)piperazine, and 17 mg (0.05 mmol) of O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) were combined in 1.0 mL dimethyl formamide and stirred at room temperature for 48 hours. To the crude reaction was added 200 μL of a 50% w/v potassium hydroxide (aqueous) solution and the mixture was stirred for 24 hours at room temperature. The reaction was neutralized by adding a few drops of acetic acid, filtered through a 0.45 μm syringe filter, and then purified by mass-triggered reverse phase HPLC in a gradient of acetonitrile and water (containing 0.1% formic acid). The clean fractions were lyophilized to afford 5.0 mg (0.01 mmol, 21% yield) of {2-amino-3-fluoro-5-[3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-[4-(2-diethylamino-ethyl)-piperazin-1-yl]-methanone as a orange glass. 1H NMR (500 MHz, MeOD) δ 8.40 (d, 1H), 8.17 (d, 1H), 7.65 (s, 1H), 7.58 (dd, 1H), 7.42 (dd, 1H), 7.31 (t, 1H), 7.22 (d, 1H), 7.14 (d, 1H), 7.07 (t, 1H), 3.86 (s, 3H), 3.70 (s, br., 4H), 2.58 (m, 12H), 1.09 (t, 6H). MS: m/z 545.3 (M+H+).

Workup

  1. customTo the crude reaction
  2. stirringthe mixture was stirred for 24 hours at room temperature
  3. filtrationfiltered through a 0.45 μm syringe
  4. filtrationfilter
  5. custompurified by mass-triggered reverse phase HPLC in a gradient of acetonitrile and water (containing 0.1% formic acid)

Sources & evidence

ORD record
ord-23ddd5e16eec4775b2c0184093d35036
Source dataset
uspto-grants-2010_05
Patent number
US07709645B2

Reaction notes

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