1-Hydroxybenzotriazole → 4-[(9-cyclopentyl-6,7,8,9-tetrahydro-5-methyl-6-oxospiro[5H-pyrimido[4,5-b][1,4]diazepine-7,1'-cyclopropan]-2-yl)amino]-3-methyl-N-(1-methyl-4-piperidinyl)benzamide

HRID 2111411

반응식

HRID 2111411 반응식
[CH:1]1([N:6]2[CH2:14][C:11]3([CH2:13][CH2:12]3)[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[CH3:31])=[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)C(C)C)C.[NH2:75][CH:76]1[CH2:81][CH2:80][N:79]([CH3:82])[CH2:78][CH2:77]1>CN(C)C=O>[CH:1]1([N:6]2[CH2:14][C:11]3([CH2:12][CH2:13]3)[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:75][CH:76]5[CH2:81][CH2:80][N:79]([CH3:82])[CH2:78][CH2:77]5)=[O:27])=[CH:24][C:23]=4[CH3:31])=[N:20][C:7]2=3)[CH2:2][CH2:3][CH2:4][CH2:5]1

참가 물질

7

반응물 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27375314-Amino-1-methylpiperidineHCID 576350414-[(9-cyclopentyl-6,7,8,9-tetrahydro-5-methyl-6-oxospiro[5H-pyrimido[4,5-b][1,4]diazepine-7,1'-cyclopropan]-2-yl)amino]-3-methylbenzoic acidHCID 178484289HCID 178484289, 화합물

생성물 1

HCID 250156054-[(9-cyclopentyl-6,7,8,9-tetrahydro-5-methyl-6-oxospiro[5H-pyrimido[4,5-b][1,4]diazepine-7,1'-cyclopropan]-2-yl)amino]-3-methyl-N-(1-methyl-4-piperidinyl)benzamide수율 65.4%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a suspension of 0.0262 g (0.000062 mole) of 4-[(9-cyclopentyl-6,7,8,9-tetrahydro-5-methyl-6-oxospiro[5H-pyrimido[4,5-b][1,4]diazepine-7,1′-cyclopropan]-2-yl)amino]-3-methylbenzoic acid (I-60) in 3 mL of dimethylformamide was added 0.0144 g (0.000107 mole) of 1-hydroxybenzotriazole, 0.0365 g (0.000096 mole) of 1-[bis(dimethylamino)methylene]-1H-benzotriazolium 3-oxide hexafluorophosphate and 0.07 mL (0.000402 mole) of ethyldiisopropylamine. The mixture was stirred for 20 minutes and then 0.012 g (0.0001 mole) of 4-amino-1-methylpiperidine was added. The mixture was stirred for an additional 2.5 hours and then concentrated under reduced pressure. The residue was dissolved in ethyl acetate and washed successively with 1 M sodium hydroxide, brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with dichloromethane-methanol (98:2-80:20) to give 0.021 g of 4-[(9-cyclopentyl-6,7,8,9-tetrahydro-5-methyl-6-oxospiro[5H-pyrimido[4,5-b][1,4]diazepine-7,1′-cyclopropan]-2-yl)amino]-3-methyl-N-(1-methyl-4-piperidinyl)benzamide (I-61)

후처리

  1. stirringThe mixture was stirred for an additional 2.5 hours
  2. concentrationconcentrated under reduced pressure
  3. dissolutionThe residue was dissolved in ethyl acetate
  4. washwashed successively with 1 M sodium hydroxide, brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel chromatography
  9. washeluting with dichloromethane-methanol (98:2-80:20)

출처 및 근거

ORD 기록
ord-7dc04268ac8e450d90576217e7acd4cd
출처 데이터셋
uspto-grants-2009_04
특허 번호
US07517873B2

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