Sodium Iodide → Formic acid N-(6-{6-chloro-5-[(methylsulfonyl)amino]-3-pyridinyl}-1H-indazol-4-yl)-2-(4-morpholinylmethyl)-1,3-thiazole-4-carboxamide

HRID 1695774Notes

Reaction equation

HRID 1695774 reaction equation
Cl[CH2:2][C:3]1[S:4][CH:5]=[C:6]([C:8]([NH:10][C:11]2[CH:19]=[C:18]([C:20]3[CH:21]=[N:22][C:23]([Cl:31])=[C:24]([NH:26][S:27]([CH3:30])(=[O:29])=[O:28])[CH:25]=3)[CH:17]=[C:16]3[C:12]=2[CH:13]=[N:14][N:15]3S(C2C=CC=CC=2)(=O)=O)=[O:9])[N:7]=1.[NH:41]1[CH2:46][CH2:45][O:44][CH2:43][CH2:42]1.CCN(C(C)C)C(C)C.[I-].[Na+].C[Si](C)(C)[O-].[K+]>CC#N.C1COCC1>[CH:8]([OH:9])=[O:44].[Cl:31][C:23]1[N:22]=[CH:21][C:20]([C:18]2[CH:17]=[C:16]3[C:12]([CH:13]=[N:14][NH:15]3)=[C:11]([NH:10][C:8]([C:6]3[N:7]=[C:3]([CH2:2][N:41]4[CH2:46][CH2:45][O:44][CH2:43][CH2:42]4)[S:4][CH:5]=3)=[O:9])[CH:19]=2)=[CH:25][C:24]=1[NH:26][S:27]([CH3:30])(=[O:29])=[O:28]

Participants

8

Reactant 5

HCID 5238Sodium IodideHCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 23668039Potassium trimethylsilanolateHCID 582558462-(Chloromethyl)-N-[6-{6-chloro-5-[(methylsulfonyl)amino]-3-pyridinyl}-1-(phenylsulfonyl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamide

Product 1

HCID 86653308Formic acid N-(6-{6-chloro-5-[(methylsulfonyl)amino]-3-pyridinyl}-1H-indazol-4-yl)-2-(4-morpholinylmethyl)-1,3-thiazole-4-carboxamide

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

2-(Chloromethyl)-N-[6-{6-chloro-5-[(methylsulfonyl)amino]-3-pyridinyl}-1-(phenylsulfonyl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamide (50 mg, 0.078 mmol) was dissolved in MeCN (0.5 ml) and added to morpholine (0.1 mmol). DIPEA (0.026 ml, 0.15 mmol) was added followed by sodium iodide (0.015 g, 0.1 mmol) and the solutions was stirred for 18 hr at 70° C. Potassium trimethylsilanolate (64 mg, 0.5 mmol) was dissolved in THF (0.25 ml) and added to the reaction mixture which was heated to 50° C. for 24 hr. The solution was quenched with aqueous MeCN (50:50, 1 ml) and neutralised. Solvent was removed in a blowdown unit. The crude residue was dissolved in DMF (200 μl), Acetone (200 μl) and water (20 μl) and purified by MDAP (Method D). The solvent was removed in vacuo using the Genevac to give the title compound.

Workup

  1. additionadded to the reaction mixture which
  2. temperaturewas heated to 50° C. for 24 hr
  3. customThe solution was quenched with aqueous MeCN (50:50, 1 ml)
  4. customSolvent was removed in a blowdown unit
  5. dissolutionThe crude residue was dissolved in DMF (200 μl)
  6. customAcetone (200 μl) and water (20 μl) and purified by MDAP (Method D)
  7. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-87a97b2e644045129d9808dab7d8e738
Source dataset
uspto-grants-2012_04
Patent number
US08163743B2

Reaction notes

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