N,N-Diethyl-2-(piperazin-1-yl)ethan-1-amine → {2-amino-3-fluoro-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-[4-(2-diethylamino-ethyl)-piperazin-1-yl]-methanone

HRID 2234637Notes

Reaction equation

HRID 2234637 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:29]([C:32]4[CH:37]=[CH:36][C:35]([CH3:38])=[CH:34][CH:33]=4)(=[O:31])=[O:30])[C:15]3=[N:16][CH:17]=2)=[CH:7][C:3]=1[C:4]([OH:6])=O.[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>CN(C)C=O>[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:29]([C:32]4[CH:33]=[CH:34][C:35]([CH3:38])=[CH:36][CH:37]=4)(=[O:31])=[O:30])[C:15]3=[N:16][CH:17]=2)=[CH:7][C:3]=1[C:4]([N:47]1[CH2:48][CH2:49][N:44]([CH2:43][CH2:42][N:41]([CH2:50][CH3:51])[CH2:39][CH3:40])[CH2:45][CH2:46]1)=[O:6]

Participants

5

Reactant 3

HCID 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 57731559{2-amino-3-fluoro-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-[4-(2-diethylamino-ethyl)-piperazin-1-yl]-methanoneYield 58.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

300 mg (0.564 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, 105 mg (0.564 mmol) of 1-(2-diethylaminoethyl)piperazine, and 279 mg of O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) were combined in 3.5 mL dimethyl formamide and stirred at room temperature for 48 hours. The reaction was extracted into ethyl acetate and washed with water. The water layer was back extracted three times with ethyl acetate. The layers were separated and the organic layer was dried over sodium sulfate and concentrated to dryness. The resulting residue was purified by flash chromatography on silica gel using a gradient of ethyl acetate (containing 10% methanol) and hexanes. The clean fractions containing the purified intermediate were evaporated to afford 230 mg (0.329 mmol, 58% yield) of {2-amino-3-fluoro-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-[4-(2-diethylamino-ethyl)-piperazin-1-yl]-methanone as a white solid. 1H NMR (500 MHz, CD3CN) δ 8.59 (d, 1H), 8.09 (s, 1H), 8.09 (d, 2H), 8.01 (s, 1H), 7.61 (dd, 1H), 7.43 (m, 4H), 7.23 (d, 1H), 7.18 (d, 1H), 7.11 (t, 1H), 4.67 (s, 2H), 3.88 (s, 3H), 3.60 (s, br., 4H), 2.52 (m, 12H), 0.99 (t, 6H); MS: m/z 699.3 (M+H+).

Workup

  1. extractionThe reaction was extracted into ethyl acetate
  2. washwashed with water
  3. extractionThe water layer was back extracted three times with ethyl acetate
  4. customThe layers were separated
  5. dry with materialthe organic layer was dried over sodium sulfate
  6. concentrationconcentrated to dryness
  7. customThe resulting residue was purified by flash chromatography on silica gel using a gradient of ethyl acetate (containing 10% methanol) and hexanes
  8. additionThe clean fractions containing the purified intermediate
  9. customwere evaporated

Sources & evidence

ORD record
ord-3e8cdb6c12b344fc9be18a5db5180938
Source dataset
uspto-grants-2010_05
Patent number
US07709645B2

Reaction notes

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