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Diisopropylethylamine → N-(5,6-dihydrothiazolo[2,3-c][1,2,4]triazol-3-yl)-2-(3-(4-(4-methoxybenzoyl)piperidin-1-yl)-2-oxopyrrolidin-1-yl)acetamide

HRID 1752274
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HRID 1752274 반응식
[CH3:1][O:2][C:3]1[CH:26]=[CH:25][C:6]([C:7]([CH:9]2[CH2:14][CH2:13][N:12]([CH:15]3[CH2:19][CH2:18][N:17]([CH2:20][C:21](O)=[O:22])[C:16]3=[O:24])[CH2:11][CH2:10]2)=[O:8])=[CH:5][CH:4]=1.Br.[N:28]1[N:29]=[C:30]([NH2:36])[N:31]2[CH2:35][CH2:34][S:33][C:32]=12.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl>[N:28]1[N:29]=[C:30]([NH:36][C:21](=[O:22])[CH2:20][N:17]2[CH2:18][CH2:19][CH:15]([N:12]3[CH2:13][CH2:14][CH:9]([C:7](=[O:8])[C:6]4[CH:25]=[CH:26][C:3]([O:2][CH3:1])=[CH:4][CH:5]=4)[CH2:10][CH2:11]3)[C:16]2=[O:24])[N:31]2[CH2:35][CH2:34][S:33][C:32]=12
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참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 712122945,6-Dihydrothiazolo[2,3-c][1,2,4]triazol-3-amine hydrobromideHCID 712123312-(3-(4-(4-Methoxybenzoyl)piperidin-1-yl)-2-oxopyrrolidin-1-yl)acetic acid

생성물 1

HCID 71212159
N-(5,6-dihydrothiazolo[2,3-c][1,2,4]triazol-3-yl)-2-(3-(4-(4-methoxybenzoyl)piperidin-1-yl)-2-oxopyrrolidin-1-yl)acetamide
수율 34.4%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

A mixture of 500 mg of 76.5% pure 2-(3-(4-(4-methoxybenzoyl)piperidin-1-yl)-2-oxopyrrolidin-1-yl)acetic acid (382 mg, 1.061 mmol) and 5,6-dihydrothiazolo[2,3-c][1,2,4]triazol-3-amine hydrobromide (237 mg, 1.061 mmol) was stirred in diisopropylethylamine (0.741 mL, 549 mg, 4.25 mmol) and dichloromethane (10 mL) before addition of HATU reagent (444 mg, 1.161 mmol). The reaction was stirred over 45 hours at room temperature. A small amount of off-white solid was removed by filtration. The filtrate was eluted through a silica gel column with 0 to 15% methanol/dichloromethane, then 15% to 30%, followed by 30%. The fractions containing contaminated product were concentrated down and eluted through a second silica gel column with 5% to 12% methanol/dichloromethane gradient followed by 12% to afford the title compound (177 mg) as a white solid. Calculated mass for C23H28N6O4S=484.57. HR-MS [m/z, (M+H)+]=485.1956. HPLC retention time=2.73 minutes (Agilent 1100 HPLC system; 3.0×100 nm 3 um C18 column; flow rate of 1.0 mL/min; gradient of 5-95% acetonitrile/water with 0.1% formic acid over 10 minutes). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.06 (br s, 1H), 7.94 (d, J=9.09 Hz, 2H), 7.03 (d, J=8.59 Hz, 2H), 3.92-4.21 (m, 6H), 3.83 (s, 3H), 3.39-3.51 (m, 1H), 3.21-3.37 (m, 3H), 2.99 (d, J=13.14 Hz, 1H), 2.64-2.84 (m, 2H), 2.28-2.42 (m, 1H), 2.03-2.18 (m, 1H), 1.85-2.02 (m, 1H), 1.65-1.78 (m, 2H), 1.44-1.60 (m, 2H).

후처리

  1. customA small amount of off-white solid was removed by filtration
  2. washThe filtrate was eluted through a silica gel column with 0 to 15% methanol/dichloromethane
  3. additionThe fractions containing contaminated product
  4. concentrationwere concentrated down
  5. washeluted through a second silica gel column with 5% to 12% methanol/dichloromethane gradient

출처 및 근거

ORD 기록
ord-d117f90c90b94c729c357acf45847d24
출처 데이터셋
uspto-grants-2015_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09163003B2

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