Sodium Carbonate → HCID 44548920、化合物

HRID 1676619ノート

反応式

HRID 1676619 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][N:7]([CH:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[C:6]=2[N:21]=1.[NH2:22][C:23]1[CH:40]=[CH:39][C:26]([C:27]([NH:29][CH:30]2[CH2:35][CH2:34][N:33]([CH2:36][CH2:37][F:38])[CH2:32][CH2:31]2)=[O:28])=[CH:25][C:24]=1[O:41][CH3:42].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C(O)(C)C.ClCCl>[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:22][C:23]4[CH:40]=[CH:39][C:26]([C:27]([NH:29][CH:30]5[CH2:31][CH2:32][N:33]([CH2:36][CH2:37][F:38])[CH2:34][CH2:35]5)=[O:28])=[CH:25][C:24]=4[O:41][CH3:42])=[N:21][C:6]2=3)[CH2:20][CH2:19][CH2:18][CH2:17]1

参加物

7

反応物 4

HCID 10340Sodium CarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 579555742-Chloro-9-cyclopentyl-7,7-difluoro-5-methyl-8,9-dihydro-5H-pyrimido[4,5-B][1,4]diazepin-6(7H)-oneHCID 580151444-amino-N-[1-(2-fluoro-ethyl)-piperidin-4-yl]-3-methoxy-benzamide

生成物 1

HCID 44548920HCID 44548920、化合物収率 55.6%

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 (0.25 mmole) of 2-chloro-9-cyclopentyl-7,7-difluoro-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-20) and 0.075 g (0.25 mmole) of 4-amino-N-[1-(2-fluoro-ethyl)-piperidin-4-yl]-3-methoxy-benzamide and 0.072 g (0.38 mmole) of p-toluenesulfonic acid monohydrate in 3 mL of isopropanol was stirred in a sealed tube at 140 degrees overnight. The mixture was cooled, and 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 three times with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by silica gel chromatography, eluting with dichloromethane-methanol (gradient, 100:0-90:10) gave 0.080 g of 4-(9-cyclopentyl-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-fluoro-ethyl)-piperidin-4-yl]-3-methoxy-benzamide (I-75).

後処理

  1. temperatureThe mixture was cooled
  2. extractionThe mixture was extracted twice with dichloromethane
  3. washThe combined organic layers were washed three times with sodium carbonate three times with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification by silica gel chromatography
  8. washeluting with dichloromethane-methanol (gradient, 100:0-90:10)

出典と根拠

ORDレコード
ord-755e9594f2564b7fb6e7a010f88648b4
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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