Diisopropylethylamine → 4-Chloro-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid {2-methyl-5-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzoylamino]-phenyl}-amide

HRID 1391478

반응식

HRID 1391478 반응식
[CH:1]1[C:5]2[C:6]([Cl:10])=[N:7][CH:8]=[N:9][C:4]=2[NH:3][CH:2]=1.ClC(Cl)(O[C:15](=[O:21])OC(Cl)(Cl)Cl)Cl.CCN(C(C)C)C(C)C.[NH2:32][C:33]1[CH:34]=[C:35]([NH:40][C:41](=[O:58])[C:42]2[CH:47]=[C:46]([C:48]([F:51])([F:50])[F:49])[CH:45]=[C:44]([N:52]3[CH:56]=[C:55]([CH3:57])[N:54]=[CH:53]3)[CH:43]=2)[CH:36]=[CH:37][C:38]=1[CH3:39]>C1COCC1>[CH3:39][C:38]1[CH:37]=[CH:36][C:35]([NH:40][C:41](=[O:58])[C:42]2[CH:47]=[C:46]([C:48]([F:49])([F:50])[F:51])[CH:45]=[C:44]([N:52]3[CH:56]=[C:55]([CH3:57])[N:54]=[CH:53]3)[CH:43]=2)=[CH:34][C:33]=1[NH:32][C:15]([N:3]1[C:4]2[N:9]=[CH:8][N:7]=[C:6]([Cl:10])[C:5]=2[CH:1]=[CH:2]1)=[O:21]

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 53566827H-Pyrrolo(2,3-d)pyrimidine, 4-chloro-HCID 68975748n-(3-Amino-4-methyl-phenyl)-3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzamide

생성물 1

HCID 596739784-Chloro-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid {2-methyl-5-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzoylamino]-phenyl}-amide수율 66%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

6-Chloro-7-deazapurine (3.9 g, 25.5 mmol), triphosgene (3.80 g, 12.8 mmol), and DIEA (8.9 mL, 51 mmol) are stirred in THF (100 mL) at 0° C. for 3 hours. The THF is removed by evaporation and the residue is dissolved in THF (100 mL). The solution is mixed with N-(3-amino-4-methyl-phenyl)-3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzamide (3.5 g, 9.3 mmol) and shaken at room temperature for 18 hours. The solvent is evaporated and the residue is purified by silica gel column chromatography (2% MeOH in CH2Cl2) to obtain 4-chloro-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid {2-methyl-5-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzoylamino]-phenyl}-amide (3.4 g, yield 65%). 1H NMR (400 MHz, DMSO-d6) δ 11.07 (s, 1H), 10.71 (s, 1H), 9.62 (s, 1H), 8.99 (s, 1H), 8.62 (s, 1H), 8.55 (s, 1H), 8.46 (d, J=4.0 Hz, 1H), 8.24 (d, J=4.0 Hz, 1H), 8.18 (s, 1H), 7.62 (d, J=8.0 Hz, 1H), 7.35 (d, J=8.0 Hz, 1H), 6.96 (d, J=4.0 Hz, 1H), 2.47 (s, 3H), 2.37 (s, 3H); ESIMS m/z 554.1 (M++1).

후처리

  1. customThe THF is removed by evaporation
  2. dissolutionthe residue is dissolved in THF (100 mL)
  3. customThe solvent is evaporated
  4. customthe residue is purified by silica gel column chromatography (2% MeOH in CH2Cl2)

출처 및 근거

ORD 기록
ord-a57a1620a23f470796431e577cff06e9
출처 데이터셋
uspto-grants-2008_03
특허 번호
US07338957B2

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