Diisopropylethylamine → HCID 69217391、化合物

HRID 2251083ノート

反応式

HRID 2251083 の反応式
[CH2:1]([O:3][C:4](=[O:35])[CH:5]=[C:6]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[Cl:34])[C:7]1[N:19]([C:20]2[C:25]([F:26])=[CH:24][CH:23]=[CH:22][C:21]=2[F:27])[C:10]2[N:11]=[C:12](S(C)(=O)=O)[N:13]=[CH:14][C:9]=2[CH:8]=1)[CH3:2].C(N(C(C)C)CC)(C)C.Cl.[NH2:46][CH:47]([CH3:52])[C:48]([CH3:51])([OH:50])[CH3:49]>CN1CCCC1=O.[NH4+].[Cl-]>[CH2:1]([O:3][C:4](=[O:35])[CH:5]=[C:6]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[Cl:34])[C:7]1[N:19]([C:20]2[C:25]([F:26])=[CH:24][CH:23]=[CH:22][C:21]=2[F:27])[C:10]2[N:11]=[C:12]([NH:46][CH:47]([CH3:52])[C:48]([OH:50])([CH3:51])[CH3:49])[N:13]=[CH:14][C:9]=2[CH:8]=1)[CH3:2]

参加物

6

反応物 3

HCID 81531DiisopropylethylamineHCID 23434633HCID 23434633、化合物2 回HCID 69218334HCID 69218334、化合物

生成物 1

HCID 69217391HCID 69217391、化合物

試薬・触媒・溶媒 2

HCID 13387N-methyl-2-pyrrolidone溶媒HCID 25517Ammonium Chloride溶媒

反応条件

温度
120 °C

実験手順

To a solution of 3-(2-chloro-phenyl)-3-[7-(2,6-difluoro-phenyl)-2-methanesulfonyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-acrylic acid ethyl ester, 14, (0.30 g, 0.59 mmol)) in N-methylpyrrolidinone (4 mL) is added diisopropylethylamine (0.41 mL, 2.36 mmol) and 3-amino-2-methyl-butan-2-ol hydrochloride salt (0.10 g, 0.71 mmol). After heating the reaction at 90° C. for 21 hours, an additional equivalent of 3-amino-2-methyl-butan-2-ol hydrochloride salt (0.08 g, 0.59 mmol) is added and the mixture heated at 120° C. for 4 hours. The reaction is cooled to room temp and then diluted with aqueous saturated NH4Cl solution. The aqueous phase is twice extracted with CHCl3 and the organic phase is then washed with aqueous saturated NaHCO3 solution. The organic phase is dried (MgSO4), filtered, concentrated in vacuo and the resulting residue is purified by preparative HPLC to afford the desired product as a yellowish solid: 1H NMR (300 MHz, d3-DMSO) δ 8.64 (s, 1H), 7.64-7.52 (m, 1H), 7.38-7.24 (m, 5H), 7.14-7.08 (m, 1H), 6.57 (s, 1H), 5.95 (s, 1H), 4.31 (bd s, NH), 3.85 (q, J=7.2 Hz, 2H), 3.34 (m, 1H), 1.04 (s, 9H), 0.93 (t, J=7.2 Hz); ESI+ MS: m/z (rel intensity) 541.0 (100, M++H).

後処理

  1. temperatureAfter heating
  2. customthe reaction at 90° C. for 21 hours
  3. temperatureThe reaction is cooled to room temp
  4. extractionThe aqueous phase is twice extracted with CHCl3
  5. washthe organic phase is then washed with aqueous saturated NaHCO3 solution
  6. dry with materialThe organic phase is dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customthe resulting residue is purified by preparative HPLC

出典と根拠

ORDレコード
ord-09116be980114e7e8d4ef8556c39e9ce
出典データセット
uspto-grants-2008_01
特許番号
US07319102B1

反応ノート

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