N,N-Dimethyl-1,3-propanediamine → 4-(9-cyclopentyl-5-propyl-7,7-difluoro-6-oxo-6,7,8,9-tetra-hydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(3-dimethylamino-propyl)-3-methoxy-benzamide

HRID 1676699

反応式

HRID 1676699 の反応式
[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH2:16][CH2:17][CH3:18])[C:8]3[CH:19]=[N:20][C:21]([NH:23][C:24]4[CH:32]=[CH:31][C:27]([C:28]([OH:30])=O)=[CH:26][C:25]=4[O:33][CH3:34])=[N:22][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.F[P-](F)(F)(F)(F)F.CN(C(N(C)C)=[N+]1C2C=CC=CC=2[N+]([O-])=N1)C.C(N(C(C)C)CC)(C)C.[CH3:68][N:69]([CH3:74])[CH2:70][CH2:71][CH2:72][NH2:73]>C(OCC)(=O)C.O.CN(C)C=O>[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH2:16][CH2:17][CH3:18])[C:8]3[CH:19]=[N:20][C:21]([NH:23][C:24]4[CH:32]=[CH:31][C:27]([C:28]([NH:73][CH2:72][CH2:71][CH2:70][N:69]([CH3:74])[CH3:68])=[O:30])=[CH:26][C:25]=4[O:33][CH3:34])=[N:22][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1

参加物

8

反応物 4

HCID 7993N,N-Dimethyl-1,3-propanediamineHCID 81531DiisopropylethylamineHCID 580150924-(9-cyclopentyl-5-propyl-7,7-difluoro-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acidHCID 178484289HCID 178484289、化合物

生成物 1

HCID 580150644-(9-cyclopentyl-5-propyl-7,7-difluoro-6-oxo-6,7,8,9-tetra-hydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(3-dimethylamino-propyl)-3-methoxy-benzamide収率 29.2%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a mixture of 0.05 g (0.11 mmole) of 4-(9-cyclopentyl-5-propyl-7,7-difluoro-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acid (I-162), 0.06 g (0.16 mmole) of 1-[bis(dimethylamino)methylene]-1H-benzotriazolium-3-oxide hexafluorophosphate and 2 mL of dimethylformamide was added 0.05 mL (0.32 mmole) of diisopropylethylamine. After stirring at room temperature for 30 minutes 0.04 mL (0.32 mmole) of 3-(dimethylamino)-propylamine was then added. The mixture was stirred at room temperature for 18 hours and then diluted with ethyl acetate and water. The aqueous phase was extracted twice with ethyl acetate. The combined organic layers were washed with water then brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with methanol-dichloromethane (gradient, 0:100-25:75) to give 0.018 g of 4-(9-cyclopentyl-5-propyl-7,7-difluoro-6-oxo-6,7,8,9-tetra-hydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(3-dimethylamino-propyl)-3-methoxy-benzamide (I-166).

後処理

  1. additionwas then added
  2. extractionThe aqueous phase was extracted twice with ethyl acetate
  3. washThe combined organic layers were washed with water
  4. dry with materialbrine, dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with methanol-dichloromethane (gradient, 0:100-25:75)

出典と根拠

ORDレコード
ord-a5bfd353c31940479f3cb3718015a44a
出典データセット
uspto-grants-2011_08
特許番号
US08003785B2

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