Methanol → HCID 86689753, 화합물

HRID 1396398노트

반응식

HRID 1396398 반응식
[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]

참가 물질

7

반응물 4

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

생성물 2

HCID 14923Ammonium HydroxideHCID 86689753HCID 86689753, 화합물수율 78.3%

시약·촉매·용매 1

HCID 13387N-methyl-2-pyrrolidone용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-6bd98dd621b7426e971d27b8e80ce361
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08901124B2

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