Water → (S)-N-{1-[4-(3-{6-[(2-Hydroxy-2-methyl-propyl)-methyl-amino]-pyridin-2-yloxy}-azetidin-1-yl)-phenyl]ethyl}-acetamide

HRID 40527

反応式

HRID 40527 の反応式
[OH:1][CH:2]1[CH2:5][N:4]([C:6]2[CH:11]=[CH:10][C:9]([C@@H:12]([NH:14][C:15](=[O:17])[CH3:16])[CH3:13])=[CH:8][CH:7]=2)[CH2:3]1.Br[C:19]1[N:24]=[C:23]([N:25]([CH3:31])[CH2:26][C:27]([CH3:30])([OH:29])[CH3:28])[CH:22]=[CH:21][CH:20]=1.CC([O-])(C)C.[Na+].O>O1CCOCC1.CN(C=O)C>[OH:29][C:27]([CH3:30])([CH3:28])[CH2:26][N:25]([CH3:31])[C:23]1[N:24]=[C:19]([O:1][CH:2]2[CH2:3][N:4]([C:6]3[CH:7]=[CH:8][C:9]([C@@H:12]([NH:14][C:15](=[O:17])[CH3:16])[CH3:13])=[CH:10][CH:11]=3)[CH2:5]2)[CH:20]=[CH:21][CH:22]=1

参加物

7

反応物 4

HCID 962WaterHCID 23676156Sodium t-butoxideHCID 793858591-[(6-Bromo-pyridin-2-yl)-methyl-amino]-2-methyl-propan-2-olHCID 86689005(S)-N-{1-[4-(3-Hydroxy-azetidin-1-yl)-phenyl]ethyl}-acetamide

生成物 1

HCID 86689028(S)-N-{1-[4-(3-{6-[(2-Hydroxy-2-methyl-propyl)-methyl-amino]-pyridin-2-yloxy}-azetidin-1-yl)-phenyl]ethyl}-acetamide

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
50 °C

実験手順

23 mg (0.10 mmol) (S)—N-{1-[4-(3-Hydroxy-azetidin-1-yl)-phenyl]ethyl}-acetamide (V.1) in 1,4-dioxane (2.0 mL) is added to 31 mg (0.12 mmol) 1-[(6-bromo-pyridin-2-yl)-methyl-amino]-2-methyl-propan-2-ol. 38 mg (0.40 mmol) NaOtBu is added followed by 7.4 mg (0.01 mmol) chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2-aminoethyl)phenyl]palladium(II). The mixture is stirred for 12 h at 50° C. 7.8 mg (0.01 mmol) chloro(2-dicyclohexylphosphino-2′,4′,6′-triisoporpyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) is added and the mixture is stirred for 12 h at 100° C. After cooling to room temperature water (0.5 mL) and DMF (2.0 mL) are added and the mixture is filtered and concentrated. The residue is purified by HPLC (acetonitrile/water (+0.1% NH4OH)) to yield the desired product.

後処理

  1. stirringthe mixture is stirred for 12 h at 100° C
  2. additionare added
  3. filtrationthe mixture is filtered
  4. concentrationconcentrated
  5. customThe residue is purified by HPLC (acetonitrile/water (+0.1% NH4OH))

出典と根拠

ORDレコード
ord-f9306f1834864021b048e47747661a2e
出典データセット
uspto-grants-2013_09
特許番号
US08530461B2

関連ノート

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