2-Aminopyridine → HCID 178511624, 화합물

HRID 1943405

반응식

HRID 1943405 반응식
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

참가 물질

7

반응물 4

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

생성물 1

HCID 178511624HCID 178511624, 화합물수율 27%

시약·촉매·용매 2

HCID 887Methanol용매HCID 8028Tetrahydrofuran용매2회

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-d61710b46ca641b386466f4cfc25f212
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08389527B2

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