Trifluoroacetic acid → HCID 178451145, 화합물

HRID 2207377노트

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HRID 2207377 반응식
Cl[C:2]1[CH:3]=[CH:4][C:5]([C:8]([C@H:11]2[CH2:16][CH2:15][C@H:14]([C:17]([O:19][CH2:20][CH2:21][CH2:22][CH3:23])=[O:18])[CH2:13][CH2:12]2)([OH:10])[CH3:9])=[N:6][CH:7]=1.[CH:24]1([C:27]2[CH:32]=[CH:31][N:30]=[C:29]([NH:33][C:34]3[CH:39]=[C:38](B4OC(C)(C)C(C)(C)O4)[CH:37]=[C:36]([CH3:49])[CH:35]=3)[N:28]=2)[CH2:26][CH2:25]1.CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.C(=O)([O-])[O-].[Na+].[Na+].C(O)(C(F)(F)F)=O>CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+].O1CCOCC1>[CH:24]1([C:27]2[CH:32]=[CH:31][N:30]=[C:29]([NH:33][C:34]3[CH:39]=[C:38]([C:2]4[CH:3]=[CH:4][C:5]([C:8]([C@H:11]5[CH2:16][CH2:15][C@H:14]([C:17]([O:19][CH2:20][CH2:21][CH2:22][CH3:23])=[O:18])[CH2:13][CH2:12]5)([OH:10])[CH3:9])=[N:6][CH:7]=4)[CH:37]=[C:36]([CH3:49])[CH:35]=3)[N:28]=2)[CH2:26][CH2:25]1

참가 물질

8

반응물 5

HCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 25112535BrettphosHCID 672563904-cyclopropyl-N-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amineHCID 178451146HCID 178451146, 화합물

생성물 1

HCID 178451145HCID 178451145, 화합물

시약·촉매·용매 2

HCID 25112666BrettPhos Palladacycle촉매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

A mixture of trans-butyl 4-(1-(5-chloropyridin-2-yl)-1-hydroxyethyl)cyclohexanecarboxylate (110 mg, 0.324 mmol), 4-cyclopropyl-N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyrimidin-2-amine (114 mg, 0.324 mmol), BrettPhos Precatalyst (13.0 mg, 0.016 mmol), BrettPhos (18.0 mg, 0.034 mmol) and sodium carbonate (330 μl, 0.660 mmol) in dioxane (1618 μl) was heated to 100° C. for 2 hours. The reaction mixture was cooled to room temperature and TFA (0.5 mL) was added. The reaction mixture was purified directly by preparative HPLC Reverse phase (C-18), eluting with Acetonitrile/Water+0.1% TFA (45-80%). The major peak was collected and lyophilized to give trans-butyl 4-(1-(5-(3-(4-cyclopropylpyrimidin-2-ylamino)-5-methylphenyl)pyridin-2-yl)-1-hydroxyethyl)cyclohexanecarboxylate as a colorless solid. MS ESI calc'd for C32H41N4O3 [M+H]+ 529. found 529.

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customThe reaction mixture was purified directly by preparative HPLC Reverse phase (C-18)
  3. washeluting with Acetonitrile/Water+0.1% TFA (45-80%)
  4. customThe major peak was collected

출처 및 근거

ORD 기록
ord-89d2ccd224fa49caa9715637f8cec75f
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09376418B2

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