Sodium Iodide → Formic acid 6-[(1,1-dioxido-4-thiomorpholinyl)methyl]-N-(6-{6-(methyloxy)-5-[(methylsulfonyl)amino]-3-pyridinyl}-1H-indazol-4-yl)-2-pyridinecarboxamide

HRID 1695781Notes

Reaction equation

HRID 1695781 reaction equation
Cl[CH2:2][C:3]1[N:8]=[C:7]([C:9]([NH:11][C:12]2[CH:20]=[C:19]([C:21]3[CH:22]=[N:23][C:24]([O:32][CH3:33])=[C:25]([NH:27][S:28]([CH3:31])(=[O:30])=[O:29])[CH:26]=3)[CH:18]=[C:17]3[C:13]=2[CH:14]=[N:15][N:16]3S(C2C=CC=CC=2)(=O)=O)=[O:10])[CH:6]=[CH:5][CH:4]=1.[NH:43]1[CH2:48][CH2:47][S:46](=[O:50])(=[O:49])[CH2:45][CH2:44]1.CCN(C(C)C)C(C)C.[I-].[Na+].C[Si](C)(C)[O-].[K+]>CC#N.C1COCC1>[CH:33]([OH:32])=[O:49].[O:49]=[S:46]1(=[O:50])[CH2:47][CH2:48][N:43]([CH2:2][C:3]2[N:8]=[C:7]([C:9]([NH:11][C:12]3[CH:20]=[C:19]([C:21]4[CH:22]=[N:23][C:24]([O:32][CH3:33])=[C:25]([NH:27][S:28]([CH3:31])(=[O:29])=[O:30])[CH:26]=4)[CH:18]=[C:17]4[C:13]=3[CH:14]=[N:15][NH:16]4)=[O:10])[CH:6]=[CH:5][CH:4]=2)[CH2:44][CH2:45]1

Participants

8

Reactant 5

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 6484228Thiomorpholine 1,1-dioxideHCID 23668039Potassium trimethylsilanolateHCID 582558006-(Chloromethyl)-N-[6-{6-(methyloxy)-5-[(methylsulfonyl)amino]-3-pyridinyl}-1-(phenylsulfonyl)-1H-indazol-4-yl]-2-pyridinecarboxamide

Product 1

HCID 67155654Formic acid 6-[(1,1-dioxido-4-thiomorpholinyl)methyl]-N-(6-{6-(methyloxy)-5-[(methylsulfonyl)amino]-3-pyridinyl}-1H-indazol-4-yl)-2-pyridinecarboxamideYield 19.8%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

6-(Chloromethyl)-N-[6-{6-(methyloxy)-5-[(methylsulfonyl)amino]-3-pyridinyl}-1-(phenylsulfonyl)-1H-indazol-4-yl]-2-pyridinecarboxamide (50 mg, 0.08 mmol) was dissolved in MeCN (0.5 ml). Thiomorpholine 1,1-dioxide (available from TCI-Europe) (14 mg, 0.1 mmol) was dissolved in MeCN (0.3 ml) and added to the mixture, followed by DIPEA (0.026 ml, 0.15 mmol) and sodium iodide (0.012 g, 0.078 mmol) (heaped microspatula). The solution was stirred and heated to 70° C. for 18 hr. Potassium trimethylsilanolate (64 mg, 0.5 mmol) was dissolved in THF (0.4 ml) and added to the mixture which was then heated at 50° C. for 5 h. The solution was quenched with aqueous MeCN (50:50, 1 ml) and neutralised, then the solvents were removed in a blowdown unit. The residue was dissolved in DMSO (0.5 ml) and purified by MDAP (Method D). The solvent was evaporated using the Genevac to give the title compound (5 mg).

Workup

  1. additionadded to the mixture
  2. additionadded to the mixture which
  3. temperaturewas then heated at 50° C. for 5 h
  4. customThe solution was quenched with aqueous MeCN (50:50, 1 ml)
  5. customneutralised, then the solvents were removed in a blowdown unit
  6. dissolutionThe residue was dissolved in DMSO (0.5 ml)
  7. custompurified by MDAP (Method D)
  8. customThe solvent was evaporated

Sources & evidence

ORD record
ord-349e397535514e7bbc1fa34d5c81d434
Source dataset
uspto-grants-2012_04
Patent number
US08163743B2

Reaction notes

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