Trifluoroacetic acid → HCID 178451145、化合物

HRID 2207377ノート

反応式

HRID 2207377 の反応式
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

参加物

8

反応物 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、化合物

生成物 1

HCID 178451145HCID 178451145、化合物

試薬・触媒・溶媒 2

HCID 25112666BrettPhos Palladacycle触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-89d2ccd224fa49caa9715637f8cec75f
出典データセット
uspto-grants-2016_06
特許番号
US09376418B2

反応ノート

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