Methanol → HCID 86689753、化合物

HRID 1396398ノート

反応式

HRID 1396398 の反応式
[C:1]([C:5]1[N:10]=[C:9]([NH:11][C:12]2[CH:17]=[C:16](Cl)[N:15]=[N:14][C:13]=2[C:19]([NH2:21])=[O:20])[CH:8]=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH2:22][C@@H:23]1[CH2:28][CH2:27][CH2:26][CH2:25][C@@H:24]1[NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33].CO.C(Cl)Cl>CN1C(=O)CCC1>[NH4+:10].[OH-:20].[C:1]([C:5]1[N:10]=[C:9]([NH:11][C:12]2[CH:17]=[C:16]([NH:22][C@@H:23]3[CH2:28][CH2:27][CH2:26][CH2:25][C@@H:24]3[NH:29][C:30](=[O:36])[O:31][C:32]([CH3:34])([CH3:33])[CH3:35])[N:15]=[N:14][C:13]=2[C:19](=[O:20])[NH2:21])[CH:8]=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

参加物

7

反応物 4

HCID 887MethanolHCID 6344DichloromethaneHCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protectedHCID 86689752HCID 86689752、化合物

生成物 2

HCID 14923Ammonium HydroxideHCID 86689753HCID 86689753、化合物収率 78.3%

試薬・触媒・溶媒 1

HCID 13387N-methyl-2-pyrrolidone溶媒

実験手順

A stirred solution of 4-(6-tert-butylpyridin-2-ylamino)-6-chloropyridazine-3-carboxamide (317 mg, 1.04 mmol) and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (444 mg, 2.07 mmol) in NMP (4 mL) was heated at 140° C. for 24 h in a sealed tube. The mixture was concentrated in vacuo (Kuglerohr, high vacuum) to a brown solid. Purification by chromatography (silica, 40 g, 0-10% of a 9:1 MeOH solution in dichloromethane, 30 min) then a second purification by chromatography (silica, 24 g, 10% acetone in dichloromethane, 10 min, then 9:1:90 MeOH:NH4OH:DCM, 10 min) gave tert-butyl (1S,2R)-2-(5-(6-tert-butylpyridin-2-ylamino)-6-carbamoylpyridazin-3-ylamino)cyclohexylcarbamate (197 mg, 407 μmol, 39%) as a brown viscous gum. MS (EI/CI) m/z: 484.2 [M+H]. This material contained small amounts of residual NMP and was used directly in the next step without further purification.

後処理

  1. concentrationThe mixture was concentrated in vacuo (Kuglerohr, high vacuum) to a brown solid
  2. customPurification by chromatography (silica, 40 g, 0-10% of a 9:1 MeOH solution in dichloromethane, 30 min)
  3. customa second purification by chromatography (silica, 24 g, 10% acetone in dichloromethane, 10 min

出典と根拠

ORDレコード
ord-6bd98dd621b7426e971d27b8e80ce361
出典データセット
uspto-grants-2014_12
特許番号
US08901124B2

反応ノート

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