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

反応式

HRID 1391478 の反応式
[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]

参加物

6

反応物 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

生成物 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}-amide収率 66%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-a57a1620a23f470796431e577cff06e9
出典データセット
uspto-grants-2008_03
特許番号
US07338957B2

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