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Hydrochloric Acid → HCID 67264342, 화합물

HRID 1040949
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HRID 1040949 반응식
[NH2:1][C:2]1[C:7]2[N:8]([CH3:14])[CH2:9][CH2:10][NH:11][C:12](=[O:13])[C:6]=2[CH:5]=[CH:4][CH:3]=1.Cl[C:16]1[N:21]=[C:20]([NH:22][C:23]2[CH:32]=[CH:31][CH:30]=[CH:29][C:24]=2[C:25]([NH:27][CH3:28])=[O:26])[C:19]([Cl:33])=[CH:18][N:17]=1.Cl>C(O)(C)C.O1CCOCC1>[Cl:33][C:19]1[C:20]([NH:22][C:23]2[CH:32]=[CH:31][CH:30]=[CH:29][C:24]=2[C:25]([NH:27][CH3:28])=[O:26])=[N:21][C:16]([NH:1][C:2]2[C:7]3[N:8]([CH3:14])[CH2:9][CH2:10][NH:11][C:12](=[O:13])[C:6]=3[CH:5]=[CH:4][CH:3]=2)=[N:17][CH:18]=1
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6

반응물 3

HCID 313Hydrochloric AcidHCID 579741322-(2,5-Dichloropyrimidin-4-ylamino)-N-methylbenzamideHCID 67263426HCID 67263426, 화합물

생성물 1

HCID 67264342HCID 67264342, 화합물수율 6.3%

시약·촉매·용매 2

HCID 3776Isopropanol용매HCID 312751,4-Dioxane
용매

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온도
110 °C

실험 절차

9-Amino-1-methyl-1,2,3,4-tetrahydro-benzo[e][1,4]diazepin-5-one (#) (40 mg, 0.21 mmol) and 2-(2,5-Dichloro-pyrimidin-4-ylamino)-N-methyl-benzamide (#) (68 mg, 0.23 mmol) were combined in isopropanol (1 mL). 4 N HCl in dioxane (57 μL) was added, and the resulting mixture was heated to 110° C. in the microwave for 20 min. The resulting mixture was filtered, washed with CH2Cl2 and acetone. The ppt was dissolved in H2O, neutralized with NaHCO3, and extracted with EtOAc, dried over MgSO4, filtered, and concentrated. The resulting residue was purified with silica gel chromatography (0-10% MeOH in CH2Cl2) to obtain 2-[5-Chloro-2-(1-methyl-5-oxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-9-ylamino)pyrimidin-4-ylamino]-N-methyl-benzamide as a white solid (6 mg, 5%). mp 282-284° C.; LCMS: m/z=452.22 (M+H+), 1H NMR (400 MHz, CDCl3) δ 11.30 (s, 1H), 8.41 (d, J=8.8 Hz, 1H), 8.06 (s, 1H), 7.73 (d, J=8.0 Hz, 1H), 7.49 (d, J=7.6 Hz, 1H), 7.42 (d, J=8.0 Hz, 1H), 7.26 (m, 1H), 7.06 (m, 1H), 6.88 (m, 1H), 6.69 (m, 1H), 6.21 (m, 1H), 4.43 (m, 1H), 3.55 (m, 2H), 3.42 (m, 2H), 3.18 (s, 3H), 3.02 (m, 3H).

후처리

  1. filtrationThe resulting mixture was filtered
  2. washwashed with CH2Cl2 and acetone
  3. dissolutionThe ppt was dissolved in H2O
  4. extractionextracted with EtOAc
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was purified with silica gel chromatography (0-10% MeOH in CH2Cl2)

출처 및 근거

ORD 기록
ord-38fa46752ec040a0aca038f8b334283a
출처 데이터셋
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08552186B2

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