1-Hydroxybenzotriazole → 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-methyl-piperidin-4-yl)-3-trifluoromethyl-benzamide

HRID 1676736ノート

反応式

HRID 1676736 の反応式
[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][C:23]=4[C:31]([F:34])([F:33])[F:32])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.ON1C2C=CC=CC=2N=N1.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.[NH2:78][CH:79]1[CH2:84][CH2:83][N:82]([CH3:85])[CH2:81][CH2:80]1>CN(C)C=O>[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26]([NH:78][CH:79]5[CH2:84][CH2:83][N:82]([CH3:85])[CH2:81][CH2:80]5)=[O:27])=[CH:24][C:23]=4[C:31]([F:33])([F:34])[F:32])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1

参加物

7

反応物 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27375314-Amino-1-methylpiperidineHCID 580150024-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-(trifluoromethyl)benzoic acidHCID 178484289HCID 178484289、化合物

生成物 1

HCID 252536784-(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-methyl-piperidin-4-yl)-3-trifluoromethyl-benzamide収率 43.5%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a mixture of 0.075 g (0.155 mmole) 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)-3-trifluoromethyl-benzoic acid (I-204) and 8 mL of dimethylformamide was added 0.0313 g (0.232 mmole) of 1-hydroxybenzotriazole, 0.0880 g (0.232 mmole) of 1-[bis(dimethylamino)methylene]-1H-benzotriazolium-3-oxide hexafluorophosphate and 0.080 g (0.617 mmole) of diisopropylethylamine. The mixture was stirred for 10 minutes, then 0.027 g (0.236 mmole) of 4-amino-1-methylpiperidine was added. The reaction mixture was stirred for 2 hours and then concentrated under reduced pressure. The residue was dissolved in 80 mL of ethyl acetate and washed three times with 10 mL of 1M sodium hydroxide, twice with 15 mL of brine, dried, filtered and concentrated under reduced pressure. Purification by silica gel chromatography, eluting with dichloromethane-methanol (gradient, 95:5-80:20) gave 0.0392 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-methyl-piperidin-4-yl)-3-trifluoromethyl-benzamide (I-205) as a white solid.

後処理

  1. stirringThe reaction mixture was stirred for 2 hours
  2. concentrationconcentrated under reduced pressure
  3. dissolutionThe residue was dissolved in 80 mL of ethyl acetate
  4. washwashed three times with 10 mL of 1M sodium hydroxide
  5. dry with materialtwice with 15 mL of brine, dried
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification by silica gel chromatography
  9. washeluting with dichloromethane-methanol (gradient, 95:5-80:20)

出典と根拠

ORDレコード
ord-50267ae7e5ef41c593ab27492c4af129
出典データセット
uspto-grants-2011_08
特許番号
US08003785B2

反応ノート

読み込み中…