Sodium Hydroxide → Sodium 5-(3,3-dimethylbut-1-ynyl)-3-(N-(4-(imidazo[1,2-b]pyridazin-6-yloxy)cyclohexyl)-4-methylcyclohexanecarboxamido)thiophene-2-carboxylate

HRID 1046434Notes

Reaction equation

HRID 1046434 reaction equation
[H-].[Na+:2].C[O:4][C:5]([C:7]1[S:8][C:9]([C:29]#[C:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[CH:10][C:11]=1[N:12]([CH:22]1[CH2:27][CH2:26][CH:25]([OH:28])[CH2:24][CH2:23]1)[C:13]([CH:15]1[CH2:20][CH2:19][CH:18]([CH3:21])[CH2:17][CH2:16]1)=[O:14])=[O:6].Cl[C:36]1[CH:37]=[CH:38][C:39]2[N:40]([CH:42]=[CH:43][N:44]=2)[N:41]=1.[OH-].[Na+]>C1COCC1>[CH3:33][C:31]([CH3:34])([CH3:32])[C:30]#[C:29][C:9]1[S:8][C:7]([C:5]([O-:4])=[O:6])=[C:11]([N:12]([CH:22]2[CH2:27][CH2:26][CH:25]([O:28][C:36]3[CH:37]=[CH:38][C:39]4[N:40]([CH:42]=[CH:43][N:44]=4)[N:41]=3)[CH2:24][CH2:23]2)[C:13]([CH:15]2[CH2:20][CH2:19][CH:18]([CH3:21])[CH2:17][CH2:16]2)=[O:14])[CH:10]=1.[Na+:2]

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 138828Imidazo(1,2-b)pyridazine, 6-chloro-HCID 58113991HCID 58113991, compound

Product 1

HCID 66850208Sodium 5-(3,3-dimethylbut-1-ynyl)-3-(N-(4-(imidazo[1,2-b]pyridazin-6-yloxy)cyclohexyl)-4-methylcyclohexanecarboxamido)thiophene-2-carboxylateYield 14%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

NaH (30 mg of a 60% oil dispersion, 0.75 mmol) was added to a solution of 5-(3,3-dimethyl-but-1-ynyl)-3-[(4-hydroxy-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester (100 mg, 0.22 mmol) and 6-chloro-imidazo[1,2-b]pyridazine (167 mg, 1.08 mmol) in THF (4.0 mL) at room temperature. The reaction was heated at 80° C. overnight, cooled, aqueous NaOH (1.0 mL of a 1.0 N solution) was added and the reaction evaporated to dryness to give a brown solid. Purification by column chromatography on reverse phase C18 silica gel (100% water to 30% acetonitrile/water) provided the desired product as a solid (17 mg, 14%) after lyophilization. MS (m/z): 563.0 [M+H]; HPLC retention time: 5.55 min (2-98% acetonitrile:water with 0.05% trifluoroacetic acid).

Workup

  1. temperaturecooled
  2. customthe reaction evaporated to dryness
  3. customto give a brown solid
  4. customPurification by column chromatography on reverse phase C18 silica gel (100% water to 30% acetonitrile/water)

Sources & evidence

ORD record
ord-86bd9d1ec75f450085682b8cbafe5a58
Source dataset
uspto-grants-2013_10
Patent number
US08569302B2

Reaction notes

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