Sodium Carbonate → 4-(7,7-difluoro-5-methyl-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 1676841ノート

反応式

HRID 1676841 の反応式
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][NH:7][C:6]=2[N:16]=1.[NH2:17][C:18]1[CH:33]=[CH:32][C:21]([C:22]([NH:24][CH:25]2[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]2)=[O:23])=[CH:20][C:19]=1[O:34][CH3:35].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl.C(O)(C)C>[F:14][C:9]1([F:15])[CH2:8][NH:7][C:6]2[N:16]=[C:2]([NH:17][C:18]3[CH:33]=[CH:32][C:21]([C:22]([NH:24][CH:25]4[CH2:26][CH2:27][N:28]([CH3:31])[CH2:29][CH2:30]4)=[O:23])=[CH:20][C:19]=3[O:34][CH3:35])[N:3]=[CH:4][C:5]=2[N:11]([CH3:12])[C:10]1=[O:13]

参加物

7

反応物 4

HCID 10340Sodium CarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 115290634-Amino-3-methoxy-n-(1-methylpiperidin-4-yl)benzamideHCID 866375242-Chloro-7,7-difluoro-5-methyl-5,7,8,9-tetrahydro-6H-pyrimido[4,5-b][1,4]diazepin-6-one

生成物 1

HCID 580150544-(7,7-difluoro-5-methyl-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収率 33.5%

試薬・触媒・溶媒 2

HCID 3776Isopropanol溶媒HCID 6344Dichloromethane溶媒

実験手順

A mixture of 0.08 g (0.32 mmole) of 2-chloro-7,7-difluoro-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-292), 0.093 g (0.35 mmole) of 4-amino-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide, 0.092 g (0.48 mmole) of p-toluenesulfonic acid monohydrate and 4 mL of isopropanol was heated in pressure tube at 120 degrees overnight. After cooling, dichloromethane and saturated sodium carbonate were added. The mixture was extracted twice with dichloromethane. The combined organic layers were washed three times with sodium carbonate, times with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by C18 reverse phase silica gel chromatography, eluting with acetonitrile-water (gradient, 10:90-100:0) to gave 0.051 g of give 4-(7,7-difluoro-5-methyl-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-303) as a white solid.

後処理

  1. temperaturewas heated in pressure tube at 120 degrees overnight
  2. temperatureAfter cooling
  3. extractionThe mixture was extracted twice with dichloromethane
  4. washThe combined organic layers were washed three times with sodium carbonate, times with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by C18 reverse phase silica gel chromatography
  9. washeluting with acetonitrile-water (gradient, 10:90-100:0)

出典と根拠

ORDレコード
ord-2e92283cd5db4d59920733ccb95d768d
出典データセット
uspto-grants-2011_08
特許番号
US08003785B2

反応ノート

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