1-Methylpiperazine → 2-{[(2R,6S)-2,6-Dimethyl-4-morpholinyl]methyl}-N-{6-[6-(methyloxy)-5-({[2-(4-methyl-1-piperazinyl)ethyl]sulfonyl}amino)-3-pyridinyl]-1H-indazol-4-yl}-1,3-thiazole-4-carboxamide

HRID 1695791Notes

Reaction equation

HRID 1695791 reaction equation
[CH3:1][C@H:2]1[O:7][C@@H:6]([CH3:8])[CH2:5][N:4]([CH2:9][C:10]2[S:11][CH:12]=[C:13]([C:15]([NH:17][C:18]3[C:19]4[C:23]([CH:24]=[C:25]([C:27]5[CH:28]=[N:29][C:30]([O:39][CH3:40])=[C:31]([NH:33][S:34]([CH:37]=[CH2:38])(=[O:36])=[O:35])[CH:32]=5)[CH:26]=3)=[N:22][N:21](C3CCCCO3)[CH:20]=4)=[O:16])[N:14]=2)[CH2:3]1.[CH3:47][N:48]1[CH2:53][CH2:52][NH:51][CH2:50][CH2:49]1>C(#N)C>[CH3:8][C@H:6]1[O:7][C@@H:2]([CH3:1])[CH2:3][N:4]([CH2:9][C:10]2[S:11][CH:12]=[C:13]([C:15]([NH:17][C:18]3[CH:26]=[C:25]([C:27]4[CH:28]=[N:29][C:30]([O:39][CH3:40])=[C:31]([NH:33][S:34]([CH2:37][CH2:38][N:51]5[CH2:52][CH2:53][N:48]([CH3:47])[CH2:49][CH2:50]5)(=[O:35])=[O:36])[CH:32]=4)[CH:24]=[C:23]4[C:19]=3[CH:20]=[N:21][NH:22]4)=[O:16])[N:14]=2)[CH2:5]1

Participants

4

Reactant 2

HCID 531671-MethylpiperazineHCID 669112332-{[(2R,6S)-2,6-Dimethyl-4-morpholinyl]methyl}-N-[6-[5-[(ethenylsulfonyl)amino]-6-(methyloxy)-3-pyridinyl]-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-yl]-1,3-thiazole-4-carboxamide

Product 1

HCID 445400352-{[(2R,6S)-2,6-Dimethyl-4-morpholinyl]methyl}-N-{6-[6-(methyloxy)-5-({[2-(4-methyl-1-piperazinyl)ethyl]sulfonyl}amino)-3-pyridinyl]-1H-indazol-4-yl}-1,3-thiazole-4-carboxamide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Acetonitrile (10 ml) was added to 2-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-N-[6-[5-[(ethenylsulfonyl)amino]-6-(methyloxy)-3-pyridinyl]-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-yl]-1,3-thiazole-4-carboxamide (250 mg) followed by 1-methylpiperazine (0.33 ml). The reaction was stirred at RT for 3 hours. The reaction was evaporated to dryness and the residue was separated between DCM and water. The DCM was passed through a hydrophobic frit then evaporated to dryness. The residue was dissolved in DMSO:methanol (1:1, v/v, 2 ml) and purified by MDAP (method E). Pure fractions were combined and evaporated to dryness. Analysis showed complete deprotection on dry-down to give title compound (116 mg).

Workup

  1. customThe reaction was evaporated to dryness
  2. customthe residue was separated between DCM and water
  3. customthen evaporated to dryness
  4. dissolutionThe residue was dissolved in DMSO:methanol (1:1, v/v, 2 ml)
  5. custompurified by MDAP (method E)
  6. customevaporated to dryness
  7. customon dry-down

Sources & evidence

ORD record
ord-7f8d81f67b8744c6a647ce9627fba134
Source dataset
uspto-grants-2012_04
Patent number
US08163743B2

Reaction notes

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