2-Aminopyridine → HCID 178511624、化合物

HRID 1943405

反応式

HRID 1943405 の反応式
Cl[C:2]1[CH:3]=[C:4](Cl)[C:5]2[N:6]([C:8]([C:11]([NH:13][C:14]3[CH:19]=[CH:18][N:17]=[CH:16][C:15]=3[F:20])=[O:12])=[CH:9][N:10]=2)[N:7]=1.[N:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[NH2:28].CC(C)([O-])C.[K+].[C@H:35]1([NH2:42])[CH2:40][CH2:39][C@H:38]([NH2:41])[CH2:37][CH2:36]1>C1COCC1.CO>[NH2:41][C@H:38]1[CH2:39][CH2:40][C@H:35]([NH:42][C:2]2[CH:3]=[C:4]([NH:28][C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][N:22]=3)[C:5]3[N:6]([C:8]([C:11]([NH:13][C:14]4[CH:19]=[CH:18][N:17]=[CH:16][C:15]=4[F:20])=[O:12])=[CH:9][N:10]=3)[N:7]=2)[CH2:36][CH2:37]1

参加物

7

反応物 4

HCID 104392-AminopyridineHCID 23665647Potassium tert-butoxideHCID 596245496,8-Dichloro-N-(3-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamideHCID 178511674HCID 178511674、化合物

生成物 1

HCID 178511624HCID 178511624、化合物収率 27%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

A suspension of 6,8-dichloro-N-(3-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide (100 mg, 0.307 mmol) in THF (1 mL) was treated with pyridin-2-amine (57.7 mg, 0.613 mmol). A solution of potassium tert-butoxide (0.613 mL, 0.613 mmol) in THF was added and the reaction was stirred at room temperature. The solvent was removed under a stream of nitrogen and the residue was taken up in MeOH and filtered. The solid material was dried under vacuum. The material was taken up in NMP (2 mL) and transferred to a microwave vial. (trans)-Cyclohexane-1,4-diamine (0.350 g, 3.07 mmol) was added and the reaction was irradiated at 300 W power, 110° C. for 40 minutes. After cooling, the crude material was diluted with 2 mL of MeOH and purified via preparative HPLC using a YMC ODS C-18 30×250 mm column with 10-100% B (Solvent A: 10% aq MeOH with 0.1% TFA; Solvent B: 90% aq. MeOH with 0.1% TFA) and a linear gradient over 60 min at 25 mL/min, monitoring at 220 nm, and a total run time of 70 min. (RT of desired=45.100 min). The appropriate fractions were concentrated under reduced pressure and lyophilized overnight, furnishing 6-((trans)-4-aminocyclohexylamino)-N-(3-fluoropyridin-4-yl)-8-(pyridin-2-ylamino)imidazo[1,2-b]pyridazine-3-carboxamide (0.057 g, 0.083 mmol) as a white, fluffy solid. LC/MS, m/z 462.3 (M+1). HPLC Rt=3.345 min. YMC S5 ODS-A column (4.6×50 mm) 0%-100% B. Solvent B: (90% MeOH, 10% H2O, 0.2% H3PO4). Solvent A: (10% MeOH, 90% H2O, 0.2% H3PO4). Gradient, start % B=0, final % B=100, gradient time 4 min, hold at 100% 1 min, flow rate 4 mL/min.

後処理

  1. customThe solvent was removed under a stream of nitrogen
  2. filtrationfiltered
  3. customThe solid material was dried under vacuum
  4. customthe reaction was irradiated at 300 W power, 110° C. for 40 minutes
  5. temperatureAfter cooling
  6. custompurified via preparative HPLC
  7. customa total run time of 70 min. (RT of desired=45.100 min)
  8. concentrationThe appropriate fractions were concentrated under reduced pressure
  9. waitlyophilized overnight

出典と根拠

ORDレコード
ord-d61710b46ca641b386466f4cfc25f212
出典データセット
uspto-grants-2013_03
特許番号
US08389527B2

関連ノート

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