6-bromo-3-[(1S,2S)-2-hydroxycyclohexyl]-10-methyl-7,8,9,10-tetrahydropyrido[3,2-h]quinazolin-4(3H)-one → 6-[(6-chloropyridin-3-yl)methyl]-3-[(1S,2S)-2-hydroxycyclohexyl]-10-methyl-7,8,9,10-tetrahydropyrido[3,2-h]quinazolin-4(3H)-one

HRID 925625ノート

反応式

HRID 925625 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:9](=[C:10]3[N:15]([CH3:16])[CH2:14][CH2:13][CH2:12][C:11]=13)[N:8]=[CH:7][N:6]([C@H:17]1[CH2:22][CH2:21][CH2:20][CH2:19][C@@H:18]1[OH:23])[C:5]2=[O:24].[Cl-].[Cl:26][C:27]1[CH:32]=[CH:31][C:30]([CH2:33][Zn+])=[CH:29][N:28]=1>C1COCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[Cl:26][C:27]1[N:28]=[CH:29][C:30]([CH2:33][C:2]2[CH:3]=[C:4]3[C:9](=[C:10]4[N:15]([CH3:16])[CH2:14][CH2:13][CH2:12][C:11]=24)[N:8]=[CH:7][N:6]([C@H:17]2[CH2:22][CH2:21][CH2:20][CH2:19][C@@H:18]2[OH:23])[C:5]3=[O:24])=[CH:31][CH:32]=1

参加物

5

反応物 2

HCID 710421236-bromo-3-[(1S,2S)-2-hydroxycyclohexyl]-10-methyl-7,8,9,10-tetrahydropyrido[3,2-h]quinazolin-4(3H)-oneHCID 178478124HCID 178478124、化合物

生成物 1

HCID 714717346-[(6-chloropyridin-3-yl)methyl]-3-[(1S,2S)-2-hydroxycyclohexyl]-10-methyl-7,8,9,10-tetrahydropyrido[3,2-h]quinazolin-4(3H)-one

試薬・触媒・溶媒 2

HCID 178418851HCID 178418851、化合物触媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 6-bromo-3-[(1S,2S)-2-hydroxycyclohexyl]-10-methyl-7,8,9,10-tetrahydropyrido[3,2-h]quinazolin-4(3H)-one (40 mg, 0.10 mmol) in THF (0.4 mL) at 0° C. was added (2-chloro-5-pyridyl)methylzinc chloride (0.5 M in THF, 408 μL, 0.20 mmol) and Pd(PtBu3)2. The mixture was warmed to rt and stirred for 30 min. The resulting solution was quenched with water and extracted with CH2Cl2. The combined extracts were dried (Na2SO4) and concentrated. Purification by silica gel chromatography (0-5% MeOH/CH2Cl2) afforded 6-[(6-chloropyridin-3-yl)methyl]-3-[(1S,2S)-2-hydroxycyclohexyl]-10-methyl-7,8,9,10-tetrahydropyrido[3,2-h]quinazolin-4(3H)-one in pure form: 1H NMR (400 MHz, CD3OD); 1H NMR (400 MHz, CDCl3) 8.20 (d, J=2.3 Hz, 1H), 8.03 (s, 1H), 7.59 (s, 1H), 7.33 (dd, J=2.3, 8.2 Hz, 1H), 7.17 (d, J=8.2 Hz, 1H), 4.51 (m, 1H), 3.96 (s, 2H), 3.90 (m, 1H), 3.12 (t, J=5.2 Hz, 2H), 3.08 (s, 3H), 2.56 (t, J=6.5 Hz, 2H), 2.24-2.15 (m, 2H), 2.00-1.92 (m, 2H), 1.89-1.75 (m, 4H), 1.55-1.37 (m, 2H); HRMS (MH+) calcd for C24H28ClN4O2 439.1895. found 439.1894.

後処理

  1. customThe resulting solution was quenched with water
  2. extractionextracted with CH2Cl2
  3. dry with materialThe combined extracts were dried (Na2SO4)
  4. concentrationconcentrated
  5. customPurification by silica gel chromatography (0-5% MeOH/CH2Cl2)

出典と根拠

ORDレコード
ord-6d8db76fead54a209f70badc2adbf36c
出典データセット
uspto-grants-2016_03
特許番号
US09284312B2

反応ノート

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