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 1695776ノート

反応式

HRID 1695776 の反応式
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

参加物

8

反応物 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

生成物 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-carboxamide収率 76.9%

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒2 回HCID 8028Tetrahydrofuran溶媒

反応条件

温度
70 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-18f915daeaa64427894311e82d6439ef
出典データセット
uspto-grants-2012_04
特許番号
US08163743B2

反応ノート

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