2-Methylbenzenesulfonic acid hydrate → 4-(9-cyclohexyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(1-(2-hydroxyethyl)piperidin-4-yl)-3-methoxybenzamide

HRID 1676798노트

반응식

HRID 1676798 반응식
Cl[C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[C:9]([F:15])([F:14])[CH2:8][N:7]([CH:16]3[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)[C:6]=2[N:22]=1.O.C1(C)C(S(O)(=O)=O)=CC=CC=1.[NH2:35][C:36]1[CH:53]=[CH:52][C:39]([C:40]([NH:42][CH:43]2[CH2:48][CH2:47][N:46]([CH2:49][CH2:50][OH:51])[CH2:45][CH2:44]2)=[O:41])=[CH:38][C:37]=1[O:54][CH3:55]>C(O)(C)C>[CH:16]1([N:7]2[CH2:8][C:9]([F:15])([F:14])[C:10](=[O:13])[N:11]([CH3:12])[C:5]3[CH:4]=[N:3][C:2]([NH:35][C:36]4[CH:53]=[CH:52][C:39]([C:40]([NH:42][CH:43]5[CH2:44][CH2:45][N:46]([CH2:49][CH2:50][OH:51])[CH2:47][CH2:48]5)=[O:41])=[CH:38][C:37]=4[O:54][CH3:55])=[N:22][C:6]2=3)[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1

참가 물질

5

반응물 3

HCID 124969952-Methylbenzenesulfonic acid hydrateHCID 579555542-Chloro-9-cyclohexyl-7,7-difluoro-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-oneHCID 580150034-Amino-N-[1-(2-hydroxyethyl)-4-piperidinyl]-3-methoxybenzamide

생성물 1

HCID 252540014-(9-cyclohexyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(1-(2-hydroxyethyl)piperidin-4-yl)-3-methoxybenzamide수율 20%

시약·촉매·용매 1

HCID 3776Isopropanol용매

실험 절차

A mixture of 0.112 g (0.34 mmole) 2-chloro-9-cyclohexyl-7,7-difluoro-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-246), 0.097 g (0.51 mmole) of toluenesulfonic acid monohydrate, 0.10 g (0.34 mmole) of 4-amino-N-[1-(2-hydroxy-ethyl)-piperidin-4-yl]-3-methoxy-benzamide and 1 mL of isopropanol was heated in a sealed vessel at 170 degrees in a microwave reactor for 2 hours, cooled and concentrated under reduced pressure. The residue taken up in ethyl acetate and washed successively with 50 mL of saturated aqueous sodium bicarbonate, 50 mL of water, 50 mL of brine. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was by preparative thin layer chromatography, eluting with dichloromethane-methanol (90:10) to give 0.040 g of 4-(9-cyclohexyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-[1-(2-hydroxy-ethyl)-piperidin-4-yl]-3-methoxy-benzamide (I-267).

후처리

  1. temperaturewas heated in a sealed vessel at 170 degrees in a microwave reactor for 2 hours
  2. temperaturecooled
  3. concentrationconcentrated under reduced pressure
  4. washwashed successively with 50 mL of saturated aqueous sodium bicarbonate, 50 mL of water, 50 mL of brine
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. washeluting with dichloromethane-methanol (90:10)

출처 및 근거

ORD 기록
ord-55b4acfef06e424dba7fb72187f1c3d4
출처 데이터셋
uspto-grants-2011_08
특허 번호
US08003785B2

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