Hydrochloric Acid → 2-{[(2R,6S)-2,6-Dimethyl-4-morpholinyl]methyl}-N-(6-{6-(methyloxy)-5-[(1H-pyrazol-4-ylsulfonyl)amino]-3-pyridinyl}-1H-indazol-4-yl)-1,3-thiazole-4-carboxamide

HRID 1695790Notes

Reaction equation

HRID 1695790 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:18]=[C:17]3[C:13]([CH:14]=[N:15][N:16]3S(C3C=CC(C)=CC=3)(=O)=O)=[C:12]([NH:29][C:30]([C:32]3[N:33]=[C:34]([CH2:37][N:38]4[CH2:43][C@H:42]([CH3:44])[O:41][C@H:40]([CH3:45])[CH2:39]4)[S:35][CH:36]=3)=[O:31])[CH:11]=2)[CH:5]=[N:6][C:7]=1[O:8][CH3:9].[NH:46]1[CH:50]=[C:49]([S:51](Cl)(=[O:53])=[O:52])[CH:48]=[N:47]1.Cl.C(Cl)Cl>N1C=CC=CC=1>[CH3:45][C@H:40]1[O:41][C@@H:42]([CH3:44])[CH2:43][N:38]([CH2:37][C:34]2[S:35][CH:36]=[C:32]([C:30]([NH:29][C:12]3[CH:11]=[C:10]([C:4]4[CH:5]=[N:6][C:7]([O:8][CH3:9])=[C:2]([NH:1][S:51]([C:49]5[CH:50]=[N:46][NH:47][CH:48]=5)(=[O:53])=[O:52])[CH:3]=4)[CH:18]=[C:17]4[C:13]=3[CH:14]=[N:15][NH:16]4)=[O:31])[N:33]=2)[CH2:39]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6344DichloromethaneHCID 227331271H-pyrazole-4-sulfonyl chlorideHCID 58255776N-{6-[5-Amino-6-(methyloxy)-3-pyridinyl]-1-[(4-methylphenyl)sulfonyl]-1H-indazol-4-yl}-2-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3-thiazole-4-carboxamide

Product 1

HCID 671556532-{[(2R,6S)-2,6-Dimethyl-4-morpholinyl]methyl}-N-(6-{6-(methyloxy)-5-[(1H-pyrazol-4-ylsulfonyl)amino]-3-pyridinyl}-1H-indazol-4-yl)-1,3-thiazole-4-carboxamide

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

N-{6-[5-Amino-6-(methyloxy)-3-pyridinyl]-1-[(4-methylphenyl)sulfonyl]-1H-indazol-4-yl}-2-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3-thiazole-4-carboxamide (65 mg) was dissolved in pyridine (2 ml) and 1H-pyrazole-4-sulfonyl chloride (25 mg) was added. The reaction was stirred at RT overnight. 2M HCl (aq) (12 ml) and DCM (12 ml) were added and the reaction was vigorously stirred. The solvent was passed through a hydrophobic frit then removed under nitrogen blow down. IPA (2 ml) and 2M NaOH (aq) (1 ml) were added and the reaction was stirred at RT. The reaction was evaporated to dryness and water (1 ml) and DCM (3 ml) were added, followed by 2M HCl (aq) (1 ml). A precipitate was observed. The mixture was evaporated to dryness. The residue was purified by MDAP using the following method:

Workup

  1. stirringthe reaction was vigorously stirred
  2. customthen removed under nitrogen blow down
  3. additionIPA (2 ml) and 2M NaOH (aq) (1 ml) were added
  4. stirringthe reaction was stirred at RT
  5. customThe reaction was evaporated to dryness and water (1 ml) and DCM (3 ml)
  6. additionwere added
  7. customThe mixture was evaporated to dryness
  8. customThe residue was purified by MDAP

Sources & evidence

ORD record
ord-7c422b277f0344b98fc02112de3d2a3a
Source dataset
uspto-grants-2012_04
Patent number
US08163743B2

Reaction notes

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