Diisopropylethylamine → HCID 69217391, 화합물

HRID 2251083노트

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HRID 2251083 반응식
[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]

참가 물질

6

반응물 3

HCID 81531DiisopropylethylamineHCID 23434633HCID 23434633, 화합물2회HCID 69218334HCID 69218334, 화합물

생성물 1

HCID 69217391HCID 69217391, 화합물

시약·촉매·용매 2

HCID 13387N-methyl-2-pyrrolidone용매HCID 25517Ammonium Chloride용매

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온도
120 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-09116be980114e7e8d4ef8556c39e9ce
출처 데이터셋
uspto-grants-2008_01
특허 번호
US07319102B1

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