2,8,9-Triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo(3.3.3)undecane → Hydrochloric Acid

HRID 1811568

반응식

HRID 1811568 반응식
[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([O:20][CH3:21])=[C:18]([Cl:22])[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].[CH3:23][S:24]([C:27]1[N:32]=[CH:31][C:30]([NH2:33])=[C:29]([CH3:34])[CH:28]=1)(=[O:26])=[O:25].C(N1CCN2CCN(CC(C)C)P1N(CC(C)C)CC2)C(C)C.CC([O-])(C)C.[Na+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([O:20][CH3:21])=[C:18]([NH:33][C:30]3[CH:31]=[N:32][C:27]([S:24]([CH3:23])(=[O:26])=[O:25])=[CH:28][C:29]=3[CH3:34])[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].[ClH:22]

참가 물질

8

반응물 4

HCID 45712432,8,9-Triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo(3.3.3)undecaneHCID 23676156Sodium t-butoxideHCID 51050526Isopropyl 4-[(6-chloro-5-methoxypyrimidin-4-yl)oxy]piperidine-1-carboxylateHCID 586715824-Methyl-6-(methylsulfonyl)pyridin-3-amine

생성물 2

HCID 313Hydrochloric AcidHCID 115838194-[6-(6-Methanesulfonyl-4-methyl-pyridin-3-ylamino)-5-methoxy-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 312751,4-Dioxane용매

반응 조건

온도
120 °C

실험 절차

A mixture of 4-(6-chloro-5-methoxy-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester (570 mg, 1.73 mmol), 6-methanesulfonyl-4-methyl-pyridin-3-ylamine (272 mg, 1.46 mmol), palladium acetate (27.3 mg, 0.122 mmol), 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phospha-bicyclo[3.3.3]undecane (87 μl, 0.245 mmol), and sodium 2-methylpropan-2-olate (249 mg, 2.59 mmol) in 4.5 mL dioxane was heated under microwave irradiation at 120° C. After 4 h, mixture was purified by HPLC; fractions containing pure product were collected and concentrated. Residue was treated with 4M HCl in dioxane, concentrated, and dried under high vacuum to give 4-[6-(6-methanesulfonyl-4-methyl-pyridin-3-ylamino)-5-methoxy-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester as a white solid (HCl salt, 261 mg, 29%). 1HNMR (MeOH-d4, 400 MHz) δ 1.23-1.24 (d, J=6.2 Hz, 6H), 1.75-1.81 (m, 2H), 1.97-2.04 (m, 2H), 2.40 (s, 3H), 3.17 (s, 3H), 3.39-3.46 (m, 2H), 3.71-3.77 (m, 2H), 3.92 (s, 3H), 4.82-4.88 (m, 1H), 5.35-5.40 (m, 1H), 7.99 (s, 1H), 7.99 (s, 1H), 8.96 (s, 1H). Exact mass calculated for C21H29N5O6S 479.18 found 480.4 (MH+).

후처리

  1. custommixture was purified by HPLC
  2. additionfractions containing pure product
  3. customwere collected
  4. concentrationconcentrated
  5. additionResidue was treated with 4M HCl in dioxane
  6. concentrationconcentrated
  7. customdried under high vacuum

출처 및 근거

ORD 기록
ord-9434f1c03bf643cc926a658565da2925
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08362248B2

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