m-Chloroperbenzoic acid → 3-(((3R,4R)-3-aminotetrahydro-2H-pyran-4-yl)amino)-5-(p-tolylamino)-1,2,4-triazine-6-carboxamide

HRID 577422

반응식

HRID 577422 반응식
CS[C:3]1[N:4]=[N:5][C:6]([C:17]([NH2:19])=[O:18])=[C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)[N:8]=1.C1C=C(Cl)C=C(C(OO)=O)C=1.CCN(C(C)C)C(C)C.C(OC(=O)[NH:46][C@@H:47]1[C@H:52]([NH2:53])[CH2:51][CH2:50][O:49][CH2:48]1)(C)(C)C>CN1C(=O)CCC1.CCOC(C)=O>[NH2:46][C@@H:47]1[C@H:52]([NH:53][C:3]2[N:4]=[N:5][C:6]([C:17]([NH2:19])=[O:18])=[C:7]([NH:9][C:10]3[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=3)[N:8]=2)[CH2:51][CH2:50][O:49][CH2:48]1

참가 물질

7

반응물 4

HCID 70297m-Chloroperbenzoic acidHCID 81531DiisopropylethylamineHCID 68077633tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamateHCID 867064153-(Methylthio)-5-(p-tolylamino)-1,2,4-triazine-6-carboxamide

생성물 1

HCID 867064143-(((3R,4R)-3-aminotetrahydro-2H-pyran-4-yl)amino)-5-(p-tolylamino)-1,2,4-triazine-6-carboxamide수율 82.8%

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 13387N-methyl-2-pyrrolidone용매

실험 절차

3-(Methylthio)-5-(p-tolylamino)-1,2,4-triazine-6-carboxamide (26 mg, 0.095 mmol) was dissolved in 4 mL NMP. To it was added mCPBA (77%) (86 mg, 0.38 mmol). The mixture was stirred at RT for 1 h. To it was added DIEA (0.17 mL, 0.95 mmol) and tert-butyl((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamate (41 mg, 0.19 mmol). The mixture was stirred at 80° C. for 2 h. The mixture was diluted with 100 mL EtOAc, washed with 1N NaOH and brine, dried, concentrated in vacuo. It was then treated with neat TFA for 1 h at RT. The mixture was diluted with water and subjected to reverse phase preparative HPLC to isolate the title compound (27 mg) as HCl salt. MS found for C16H21N7O2 as (M+H)+ 344.4. UV: λ=235, 273 nm. Proton NMR: (CD3OD) δ 7.56 (2H, d, J=6.8 Hz), 7.31 (2H, d, J=7.6 Hz), 4.36 (1H, dt, J=11.6; 5.2 Hz), 4.10 (1H, dd, J=11.6; 4.8 Hz), 3.99 (1H, d, J=13.2 Hz), 3.74 (1H, s), 3.67-3.61 (2H, m), 2.38 (3H, s), 2.16 (1H, m), 1.91 (1H, m) ppm.

후처리

  1. stirringThe mixture was stirred at 80° C. for 2 h
  2. washwashed with 1N NaOH and brine
  3. customdried
  4. concentrationconcentrated in vacuo
  5. additionIt was then treated with neat TFA for 1 h at RT
  6. additionThe mixture was diluted with water

출처 및 근거

ORD 기록
ord-f7f301af22f84045bc42832c09a0a1ef
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09040530B2

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