Sodium Iodide → Formic acid 2-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-N-(6-{6-(methyloxy)-5-[(methylsulfonyl)amino]-3-pyridinyl}-1H-indazol-4-yl)-1,3-thiazole-4-carboxamide

HRID 1695776Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1695776
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]([O:31][CH3:32])=[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.[CH3:42][C@H:43]1[O:48][C@@H:47]([CH3:49])[CH2:46][NH:45][CH2:44]1.CCN(C(C)C)C(C)C.[I-].[Na+].C[Si](C)(C)[O-].[K+]>CC#N.C1COCC1>[CH:32]([OH:31])=[O:48].[CH3:49][C@H:47]1[O:48][C@@H:43]([CH3:42])[CH2:44][N:45]([CH2:2][C:3]2[S:4][CH:5]=[C:6]([C:8]([NH:10][C:11]3[CH:19]=[C:18]([C:20]4[CH:21]=[N:22][C:23]([O:31][CH3:32])=[C:24]([NH:26][S:27]([CH3:30])(=[O:29])=[O:28])[CH:25]=4)[CH:17]=[C:16]4[C:12]=3[CH:13]=[N:14][NH:15]4)=[O:9])[N:7]=2)[CH2:46]1

Komponenten

8

Edukt 5

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 6415002,6-Dimethylmorpholine, cis-HCID 23668039Potassium trimethylsilanolateHCID 582557402-(Chloromethyl)-N-[6-{6-(methyloxy)-5-[(methylsulfonyl)amino]-3-pyridinyl}-1-(phenylsulfonyl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamide

Produkt 1

HCID 67155589Formic acid 2-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-N-(6-{6-(methyloxy)-5-[(methylsulfonyl)amino]-3-pyridinyl}-1H-indazol-4-yl)-1,3-thiazole-4-carboxamideAusbeute 76,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6342AcetonitrileLösungsmittel2×HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

2-(Chloromethyl)-N-[6-{6-(methyloxy)-5-[(methylsulfonyl)amino]-3-pyridinyl}-1-(phenylsulfonyl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamide (50 mg, 0.08 mmol) was dissolved in MeCN (0.5 ml). (2R,6S)-2,6-Dimethylmorpholine (23 mg, 0.1 mmol, available from Lancaster Synthesis) 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 hrs. 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 (19 mg).

Aufarbeitung

  1. additionadded to the mixture
  2. additionadded to the mixture which
  3. temperaturewas then heated at 50° C. for 5 hrs
  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

Quellen und Nachweise

ORD-Eintrag
ord-18f915daeaa64427894311e82d6439ef
Quelldatensatz
uspto-grants-2012_04
Patentnummer
US08163743B2

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