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

HRID 1391480

반응식

HRID 1391480 반응식
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:26])[C:10]2[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[C:12]([N:20]3[CH:24]=[C:23]([CH3:25])[N:22]=[CH:21]3)[CH:11]=2)=[CH:4][C:3]=1[NH:27][C:28]([N:30]1[C:34]2[N:35]=[CH:36][N:37]=[C:38](Cl)[C:33]=2[CH:32]=[CH:31]1)=[O:29].Cl.Cl.[CH3:42][N:43]([CH3:51])[C:44]1[CH:49]=[CH:48][CH:47]=[C:46]([NH2:50])[CH:45]=1.C(Cl)(=O)C.NC1C=CC=CC=1>C(O)CCC>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:26])[C:10]2[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[C:12]([N:20]3[CH:24]=[C:23]([CH3:25])[N:22]=[CH:21]3)[CH:11]=2)=[CH:4][C:3]=1[NH:27][C:28]([N:30]1[C:34]2[N:35]=[CH:36][N:37]=[C:38]([NH:50][C:46]3[CH:47]=[CH:48][CH:49]=[C:44]([N:43]([CH3:51])[CH3:42])[CH:45]=3)[C:33]=2[CH:32]=[CH:31]1)=[O:29]

참가 물질

6

반응물 4

HCID 6115AnilineHCID 6367Acetyl chlorideHCID 771241,3-Benzenediamine, N1,N1-dimethyl-, hydrochloride (1:2)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

생성물 1

HCID 114907314-(3-Dimethylamino-phenylamino)-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid {2-methyl-5-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzoylamino]-phenyl}-amide수율 71%

시약·촉매·용매 1

HCID 2631-Butanol용매

반응 조건

온도
80 °C

실험 절차

4-Chloro-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid {2-methyl-5-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzoylamino]-phenyl}-amide resin (50 mg, 0.05 mmol), prepared as in reference 3, in n-butanol (2 mL) is mixed with N,N-dimethyl-1,3-phenylenediamine dihydrochloride (52.3 mg, 0.25 mmol) or mixed with acetyl chloride (17.8 μL, 0.25 mmol) and aniline and shaken at 80° C. for 24 hours. The resulting mixture is filtered and the resin is treated with TFA/CH2Cl2/H2O (45/50/5) (600 μL) for 30 minutes before filtering and washing with CH2Cl2 (3×2 mL), MeOH (3×2 mL). The washes are then combined together and concentrated. The residue is purified by preparative HPLC-MS to give 4-(3-dimethylamino-phenylamino)-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid {2-methyl-5-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzoylamino]-phenyl}-amide (23.2 mg, yield 71%); 1H NMR (400 MHz, DMSO-d6) δ 11.60 (s, 1H), 10.65 (s, 1H), 9.68 (s, 1H), 9.61 (s, 1H), 8.60 (s, 1H), 8.54 (s, 1H), 8.53 (s, 1H), 8.46 (s, 1H), 8.41 (s, 1H), 8.16 (s, 1H), 7.82 (d, J=3.9 Hz, 1H), 7.60 (d, J=8.2 Hz, 1H), 7.32 (d, J=3.6 Hz, 1H), 6.54 (d, J=8.4 Hz, 1H), 2.92 (s, 6H), 2.45 (s, 3H), 2.35 (s, 3H); ESIMS m/z 654.2 (M++1).

후처리

  1. filtrationThe resulting mixture is filtered
  2. additionthe resin is treated with TFA/CH2Cl2/H2O (45/50/5) (600 μL) for 30 minutes
  3. filtrationbefore filtering
  4. washwashing with CH2Cl2 (3×2 mL), MeOH (3×2 mL)
  5. concentrationconcentrated
  6. customThe residue is purified by preparative HPLC-MS

출처 및 근거

ORD 기록
ord-ff1086d9b24c468caba5a102124878d1
출처 데이터셋
uspto-grants-2008_03
특허 번호
US07338957B2

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