Methylamine → 2-(ethylamino)-N-[5-pyrimidin-5-yl-6-(2-quinolin-6-ylethynyl)pyridin-2-yl]butanamide

HRID 535423ノート

反応式

HRID 535423 の反応式
[N:1]1[CH:6]=[C:5]([C:7]2[CH:8]=[CH:9][C:10]([NH2:25])=[N:11][C:12]=2[C:13]#[C:14][C:15]2[CH:16]=[C:17]3[C:22](=[CH:23][CH:24]=2)[N:21]=[CH:20][CH:19]=[CH:18]3)[CH:4]=[N:3][CH:2]=1.[CH3:26][CH2:27][N:28](C(C)C)C(C)C.Br[CH:36]([CH2:40][CH3:41])[C:37](Br)=[O:38].CN>C(Cl)Cl.C1COCC1.CN1C(=O)CCC1>[CH2:27]([NH:28][CH:36]([CH2:40][CH3:41])[C:37]([NH:25][C:10]1[CH:9]=[CH:8][C:7]([C:5]2[CH:6]=[N:1][CH:2]=[N:3][CH:4]=2)=[C:12]([C:13]#[C:14][C:15]2[CH:16]=[C:17]3[C:22](=[CH:23][CH:24]=2)[N:21]=[CH:20][CH:19]=[CH:18]3)[N:11]=1)=[O:38])[CH3:26]

参加物

8

反応物 4

HCID 6329MethylamineHCID 81531DiisopropylethylamineHCID 1172932-Bromobutanoyl bromideHCID 866944135-Pyrimidin-5-yl-6-(2-quinolin-6-ylethynyl)pyridin-2-amine

生成物 1

HCID 866944122-(ethylamino)-N-[5-pyrimidin-5-yl-6-(2-quinolin-6-ylethynyl)pyridin-2-yl]butanamide

試薬・触媒・溶媒 3

HCID 6344Dichloromethane溶媒2 回HCID 8028Tetrahydrofuran溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

実験手順

5-pyrimidin-5-yl-6-(2-quinolin-6-ylethynyl)pyridin-2-amine G2b (600 mg, 1.86 mmol) is mixed with NMP (10 ml) and DIPEA (1.42 ml, 8.35 mmol). 2-Bromobutanoyl bromide (985 μl, 8.17 mmol) is added dropwise. The mixture stirred for 1 h at RT. The mixture is diluted with DCM and extracted with a saturated aqueous solution of NaHCO3. The combined organic layers are dried over MgSO4 and concentrated in vacuo. The crude intermediate is mixed with a THF solution of methylamine (2 mol/l, 5 ml, 10 mmol) and stirred at RT for 16 h. The mixture is diluted with DCM and extracted with a saturated aqueous solution of NaHCO3. The combined organic layers are dried over MgSO4 and concentrated in vacuo. The product is purified by RP HPLC. Yield: 250 mg (32%). HPLC-MS: M+H=423; tR=1.25 min (*Method—1).

後処理

  1. extractionextracted with a saturated aqueous solution of NaHCO3
  2. dry with materialThe combined organic layers are dried over MgSO4
  3. concentrationconcentrated in vacuo
  4. stirringstirred at RT for 16 h
  5. extractionextracted with a saturated aqueous solution of NaHCO3
  6. dry with materialThe combined organic layers are dried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe product is purified by RP HPLC

出典と根拠

ORDレコード
ord-c2813ae979d3436c916f4e26cc601651
出典データセット
uspto-grants-2014_10
特許番号
US08859541B2

反応ノート

読み込み中…