p-Toluenesulfonic acid monohydrate → 3-methoxy-4-[[6-(1-methoxypropan-2-yl)-2-methyl-3-oxo-2,6,8,10-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-9-yl]amino]-N-(1-methyl-4-piperidyl)benzamide

HRID 2234287노트

반응식

HRID 2234287 반응식
Cl[C:2]1[N:12]=[C:11]2[C:5]([N:6]([CH3:19])[C:7](=[O:18])[CH2:8][CH2:9][N:10]2[CH:13]([CH3:17])[CH2:14][O:15][CH3:16])=[CH:4][N:3]=1.[NH2:20][C:21]1[CH:36]=[CH:35][C:24]([C:25]([NH:27][CH:28]2[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]2)=[O:26])=[CH:23][C:22]=1[O:37][CH3:38].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(C)CC(O)C.CO>[CH3:38][O:37][C:22]1[CH:23]=[C:24]([CH:35]=[CH:36][C:21]=1[NH:20][C:2]1[N:12]=[C:11]2[C:5](=[CH:4][N:3]=1)[N:6]([CH3:19])[C:7](=[O:18])[CH2:8][CH2:9][N:10]2[CH:13]([CH3:17])[CH2:14][O:15][CH3:16])[C:25]([NH:27][CH:28]1[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]1)=[O:26]

참가 물질

6

반응물 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 115290634-Amino-3-methoxy-n-(1-methylpiperidin-4-yl)benzamideHCID 8661754510-Chloro-2-(1-methoxypropan-2-yl)-6-methyl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one2회

생성물 1

HCID 686835153-methoxy-4-[[6-(1-methoxypropan-2-yl)-2-methyl-3-oxo-2,6,8,10-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-9-yl]amino]-N-(1-methyl-4-piperidyl)benzamide

시약·촉매·용매 2

HCID 887Methanol용매2회HCID 79104-Methyl-2-Pentanol용매

반응 조건

온도
100 °C

실험 절차

10-chloro-2-(1-methoxypropan-2-yl)-6-methyl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one (Intermediate 112 60 mg, 0.21 mmol), 4-amino-3-methoxy-N-(1-methyl-4-piperidyl)benzamide (WO06/018220; 56 mg, 0.21 mmol), and p-toluenesulphonic acid monohydrate (100 mg, 0.53 mmol) were combined in 4-Methyl-2-pentanol (2 mL) and heated at 100° C. for 16 hrs. The reaction mixture was cooled to room temperature and dissolved in Methanol. The resultant solution was added to a 5 g SCX-3 column pre wet with MeOH (2 column volumes). Flushed with MeOH (2 column volumes) and crude product eluted with 2M ammonia in MeOH and solvents evaporated. The resultant residue was dissolved in DCM and purified on silica eluting with a gradient of 5-15% MeOH/DCM. Product containing fractions were combined and evaporated to a yellow gum which was purified by base modified reverse phase HPLC to give the title compound as a beige solid. (35 mg, 32%)

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customFlushed with MeOH (2 column volumes) and crude product
  3. washeluted with 2M ammonia in MeOH and solvents
  4. customevaporated
  5. dissolutionThe resultant residue was dissolved in DCM
  6. custompurified on silica eluting with a gradient of 5-15% MeOH/DCM
  7. additionProduct containing fractions
  8. customevaporated to a yellow gum which
  9. customwas purified by base modified reverse phase HPLC

출처 및 근거

ORD 기록
ord-4ea80e9d1ca141259182dea6cf84e18a
출처 데이터셋
uspto-grants-2010_05
특허 번호
US07709471B2

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