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 1040838ノート

反応式

HRID 1040838 の反応式
[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]

参加物

6

反応物 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

生成物 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-benzamide収率 70.1%

試薬・触媒・溶媒 2

HCID 3776Isopropanol溶媒HCID 312751,4-Dioxane溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-6b302447b8e248f390d66e2225a8c565
出典データセット
uspto-grants-2013_10
特許番号
US08552186B2

反応ノート

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