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Triethylamine → tert-butyl (1-(4-(9H-benzo[f]pyrido[2,3-b][1,2,4]triazolo[4,3-d][1,4]diazepin-3-yl)benzoyl)piperidin-4-yl)carbamate

HRID 44225
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HRID 44225 반응식
[N:1]1[N:2]=[C:3]([C:19]2[CH:27]=[CH:26][C:22]([C:23](O)=[O:24])=[CH:21][CH:20]=2)[N:4]2[C:10]=1[C:9]1[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=1[NH:7][C:6]1[N:15]=[CH:16][CH:17]=[CH:18][C:5]2=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.[NH:59]1[CH2:64][CH2:63][CH:62]([NH:65][C:66](=[O:72])[O:67][C:68]([CH3:71])([CH3:70])[CH3:69])[CH2:61][CH2:60]1>CN(C=O)C.C(OCC)(=O)C>[N:1]1[N:2]=[C:3]([C:19]2[CH:27]=[CH:26][C:22]([C:23]([N:59]3[CH2:60][CH2:61][CH:62]([NH:65][C:66](=[O:72])[O:67][C:68]([CH3:69])([CH3:71])[CH3:70])[CH2:63][CH2:64]3)=[O:24])=[CH:21][CH:20]=2)[N:4]2[C:10]=1[C:9]1[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=1[NH:7][C:6]1[N:15]=[CH:16][CH:17]=[CH:18][C:5]2=1
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참가 물질

7

반응물 4

HCID 8471TriethylamineHCID 7238334-(N-Boc-amino)piperidineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 1361637624-(9H-benzo[f]pyrido[2,3-b][1,2,4]triazolo[4,3-d][1,4]diazepin-3-yl)benzoic acid

생성물 1

HCID 136163790
tert-butyl (1-(4-(9H-benzo[f]pyrido[2,3-b][1,2,4]triazolo[4,3-d][1,4]diazepin-3-yl)benzoyl)piperidin-4-yl)carbamate

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of the 4-(9H-benzo[f]pyrido[2,3-b][1,2,4]triazolo[4,3-d][1,4]diazepin-3-yl)benzoic acid (0.5 g, 1.4 mmol) in DMF (5 mL) was added HBTU (0.56 g, 1.4 mmol) follwed by triethylamine (0.392 mL, 2.8 mmol). The reaction mixture was stirred at room temperature for 15 minutes then tert-butyl piperidin-4-ylcarbamate (0.31 g, 1.5 mmol) was added and the mixture stirred at room temperature for an additional 3 hours. The mixture was diluted with ethyl acetate (50 mL) and washed with saturated aqueous sodium bicarbonate solution (50 mL) and brine (50 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography (SiO2, gradient: 50% ethyl acetate in hexanes to 100% ethyl acetate). The tert-butyl (1-(4-(9H-benzo[f]pyrido[2,3-b][1,2,4]triazolo[4,3-d][1,4]diazepin-3-yl)benzoyl)piperidin-4-yl)carbamate was obtained as a white solid (0.478 g, 63%). M.p.=196-202° C.; 400 MHz 1H NMR (DMSO-d6) δ: 8.81 (br.s, 1H), 8.22 (dd, J=4.4, 1.6 Hz, 1H), 7.97 (dd, J=7.6, 1.6 Hz, 1H), 7.52-7.4 (m, 5H), 7.35 (d, J=8.0 Hz, 1H), 7.19 (dd, J=8.0, 1.2 Hz, 1H), 7.14 (dd, J=7.6, 1.2 Hz, 1H), 6.93 (dd, J=8.0, 1.6 Hz, 1H), 6.89 (br.s, 1H), 4.35-4.25 (m, 1H), 3.6-3.45 (m, 2H), 3.2-3.05 (m, 1H), 3.02-2.9 (m, 1H), 1.9-1.65 (m, 2H), 1.38 (s, 9H), 1.35-1.15 (m, 2H); LCMS [M+H]: 538.

후처리

  1. stirringthe mixture stirred at room temperature for an additional 3 hours
  2. washwashed with saturated aqueous sodium bicarbonate solution (50 mL) and brine (50 mL)
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by flash chromatography (SiO2, gradient: 50% ethyl acetate in hexanes to 100% ethyl acetate)

출처 및 근거

ORD 기록
ord-6e2029ba04564da5a8f309af0ef185a6
출처 데이터셋
uspto-grants-2013_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08541407B2

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