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

HRID 1695775노트

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HRID 1695775 반응식
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][CH:43]([N:45]1[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]1)[CH3:44].CCN(C(C)C)C(C)C.[I-].[Na+].C[Si](C)(C)[O-:64].[K+]>CC#N.C1COCC1>[CH:32]([OH:31])=[O:64].[CH3:42][CH:43]([N:45]1[CH2:50][CH2:49][N:48]([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)[CH2:47][CH2:46]1)[CH3:44]

참가 물질

8

반응물 5

HCID 5238Sodium IodideHCID 780131-IsopropylpiperazineHCID 81531DiisopropylethylamineHCID 23668039Potassium trimethylsilanolateHCID 582557402-(Chloromethyl)-N-[6-{6-(methyloxy)-5-[(methylsulfonyl)amino]-3-pyridinyl}-1-(phenylsulfonyl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamide

생성물 1

HCID 67156123Formic acid 2-{[4-(1-methylethyl)-1-piperazinyl]methyl}-N-(6-{6-(methyloxy)-5-[(methylsulfonyl)amino]-3-pyridinyl}-1H-indazol-4-yl)-1,3-thiazole-4-carboxamide수율 43.6%

시약·촉매·용매 2

HCID 6342Acetonitrile용매2회HCID 8028Tetrahydrofuran용매

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온도
70 °C

실험 절차

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). 4-(1-Methylethyl)piperazine (13 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 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 (11 mg).

후처리

  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

출처 및 근거

ORD 기록
ord-a07389b2a5ff45f8b545a102a52d6c46
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08163743B2

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