p-Toluenesulfonic acid monohydrate → (Rac)-4-(9-cyclobutyl-5,7-dimethyl-6-oxo-6,7,8,9-tetrahydro-5h-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-n-(1-methyl-piperidin-4-yl)-benzamide

HRID 2111380노트

반응식

HRID 2111380 반응식
Cl[C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[CH:9]([CH3:14])[CH2:8][N:7]([CH:15]3[CH2:18][CH2:17][CH2:16]3)[C:6]=2[N:19]=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(O)C>[CH:15]1([N:7]2[CH2:8][CH:9]([CH3:14])[C:10](=[O:13])[N:11]([CH3:12])[C:5]3[CH:4]=[N:3][C:2]([NH:20][C:21]4[CH:36]=[CH:35][C:24]([C:25]([NH:27][CH:28]5[CH2:29][CH2:30][N:31]([CH3:34])[CH2:32][CH2:33]5)=[O:26])=[CH:23][C:22]=4[O:37][CH3:38])=[N:19][C:6]2=3)[CH2:18][CH2:17][CH2:16]1

참가 물질

5

반응물 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 115290634-Amino-3-methoxy-n-(1-methylpiperidin-4-yl)benzamideHCID 87618676(Rac)-2-chloro-9-cyclobutyl-5,7-dimethyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one

생성물 1

HCID 25015539(Rac)-4-(9-cyclobutyl-5,7-dimethyl-6-oxo-6,7,8,9-tetrahydro-5h-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-n-(1-methyl-piperidin-4-yl)-benzamide수율 58.6%

시약·촉매·용매 1

HCID 3776Isopropanol용매

실험 절차

A solution of 0.050 g (0.00018 mole) of (rac)-2-chloro-9-cyclobutyl-5,7-dimethyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-52), 0.047 g (0.00018 mole) of 4-amino-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide, 0.053 g (0.00028 mole) of p-toluenesulfonic acid monohydrate and 4.0 mL of 2-propanol was heated at 180 degrees for 2 hours in a microwave reactor. The reaction mixture was concentrated and the residue diluted with dichloromethane and washed twice with saturated sodium bicarbonate solution. The aqueous phase was extracted with dichloromethane. The combined organic phases were washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with dichloromethane-methanol (100:0-75:25 n) to give 0.0535 g of (rac)-4-(9-cyclobutyl-5,7-dimethyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide (I-52) as white powder. HRMS (ES+) m/z Calcd for C27H37N7O3+H [(M+H)+]: 508.3031. Found: 508.3031.

후처리

  1. concentrationThe reaction mixture was concentrated
  2. additionthe residue diluted with dichloromethane
  3. washwashed twice with saturated sodium bicarbonate solution
  4. extractionThe aqueous phase was extracted with dichloromethane
  5. washThe combined organic phases were washed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel chromatography
  10. washeluting with dichloromethane-methanol (100:0-75:25 n)

출처 및 근거

ORD 기록
ord-ac7826e29e0141f2a823b9b016964e4f
출처 데이터셋
uspto-grants-2009_04
특허 번호
US07517873B2

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