Methanol → HCID 178511627, compound

HRID 1943466Notes

Reaction equation

HRID 1943466 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9]2[CH:10]=[C:11]([NH:28][C:29]3[CH:34]=[CH:33][CH:32]=[C:31](Br)[N:30]=3)[C:12]3[N:13]([C:15]([C:18]([NH:20][C:21]4[CH:26]=[CH:25][N:24]=[CH:23][C:22]=4[F:27])=[O:19])=[CH:16][N:17]=3)[N:14]=2)[CH2:4][CH2:3]1.[NH2:36][C@H:37]1[CH2:42][CH2:41][C@H:40]([OH:43])[CH2:39][CH2:38]1.CO>CN1C(=O)CCC1>[NH2:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9]2[CH:10]=[C:11]([NH:28][C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([NH:36][C@H:37]4[CH2:42][CH2:41][C@H:40]([OH:43])[CH2:39][CH2:38]4)[N:30]=3)[C:12]3[N:13]([C:15]([C:18]([NH:20][C:21]4[CH:26]=[CH:25][N:24]=[CH:23][C:22]=4[F:27])=[O:19])=[CH:16][N:17]=3)[N:14]=2)[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 887MethanolHCID 178511619HCID 178511619, compoundHCID 178511715HCID 178511715, compound

Product 1

HCID 178511627HCID 178511627, compoundYield 45.4%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of 46A (25 mg, 0.046 mmol) and (trans)-4-aminocyclohexanol (100 mg, 0.868 mmol) in NMP (0.4 mL) was heated at 160° C. in a microwave for 1.5 h (300 W), and then cooled to room temperature. The mixture was diluted by MeOH, and purified by preparative reversed-phase HPLC to give 6-((trans-4-aminocyclohexyl)amino)-N-(3-fluoro-4-pyridinyl)-8-((6-((trans-4-hydroxycyclohexyl)amino)-2-pyridinyl)amino)imidazo[1,2-b]pyridazine-3-carboxamide (12 mg, 28%) as a yellow solid. HPLC Rt=2.517 min (Chromolith SpeedROD 4.6×50 mm, 10-90% aqueous methanol containing 0.1% TFA, 4 min gradient, monitored at 220 nm), [M+H]=575.

Workup

  1. temperaturecooled to room temperature
  2. custompurified by preparative reversed-phase HPLC

Sources & evidence

ORD record
ord-c8c119953a0246258acca5cfa4934f23
Source dataset
uspto-grants-2013_03
Patent number
US08389527B2

Reaction notes

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