Hydrochloric Acid → 3-Chloro-2-[5-chloro-2-(1-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide

HRID 1040838노트

반응식

HRID 1040838 반응식
[Cl:1][C:2]1[C:3]([NH:12][C:13]2[C:18]([Cl:19])=[CH:17][N:16]=[C:15](Cl)[N:14]=2)=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([NH:7][CH3:8])=[O:6].[NH2:21][C:22]1[CH:34]=[CH:33][C:25]2[N:26]([CH3:32])[C:27](=[O:31])[CH2:28][CH2:29][CH2:30][C:24]=2[CH:23]=1.Cl>CC(O)C.O1CCOCC1>[Cl:1][C:2]1[C:3]([NH:12][C:13]2[C:18]([Cl:19])=[CH:17][N:16]=[C:15]([NH:21][C:22]3[CH:34]=[CH:33][C:25]4[N:26]([CH3:32])[C:27](=[O:31])[CH2:28][CH2:29][CH2:30][C:24]=4[CH:23]=3)[N:14]=2)=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([NH:7][CH3:8])=[O:6]

참가 물질

6

반응물 3

HCID 313Hydrochloric AcidHCID 197602587-Amino-1-methyl-1,3,4,5-tetrahydro-benzo[B]azepin-2-oneHCID 866338732-(2,5-dichloro-pyrimidin-4-ylamino)-3-chloro-N-methyl-benzamide

생성물 1

HCID 668300523-Chloro-2-[5-chloro-2-(1-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide수율 70.1%

시약·촉매·용매 2

HCID 3776Isopropanol용매HCID 312751,4-Dioxane용매

실험 절차

3-Chloro-2-(2,5-dichloro-pyrimidin-4-ylamino)-N-methyl-benzamide (36.0 mg, 0.109 mmol) and 7-amino-1-methyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (22.8 mg, 0.120 mmol) were slurried in iPrOH (1.5 mL) prior to adding ˜0.2 mL of 4N HCl in dioxane. This mixture was heated in a microwave reactor (sealed vessel) at 120° C. for 40 min. The mixture was extracted into DCM, washed with saturated aqueous NaHCO3 solution and the organic layer was dried by passing through a plug of Na2SO4. The resulting filtrate was evaporated and the residue purified by chromatography (silica gel, DCM/5% NH4OH-MeOH gradient). The appropriate fractions were combined and evaporated to afford a solid that was triturated with ether (2×2 mL) and yielded product (37.1 mg, 70%) as a yellow foam that had the following properties: m.p.=145-160° C.; LC/MS (ESI+): 485 (M+H); 1H-NMR (CDCl3, 400 MHz): δ 8.11 (s, 1H), 8.01 (s, 1H), 7.61 (d, 1H, J=8.1), 7.53 (d, 1H, J=8.1), 7.35-7.20 (m, 3H), 6.95 (m, 2H), 6.10 (br s, 1H), 3.38 (s, 3H), 2.83 (d, 3H, J=5.0), 2.55 (m, 2H), 2.24 (m, 2H), 2.09 (m, 2H).

후처리

  1. temperatureThis mixture was heated in a microwave reactor
  2. custom(sealed vessel) at 120° C. for 40 min
  3. extractionThe mixture was extracted into DCM
  4. washwashed with saturated aqueous NaHCO3 solution
  5. customthe organic layer was dried
  6. customThe resulting filtrate was evaporated
  7. customthe residue purified by chromatography (silica gel, DCM/5% NH4OH-MeOH gradient)
  8. customevaporated
  9. customto afford a solid
  10. customthat was triturated with ether (2×2 mL)

출처 및 근거

ORD 기록
ord-6b302447b8e248f390d66e2225a8c565
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08552186B2

반응 노트

불러오는 중…