Tetrahydrofuran → HCID 67373952, compound

HRID 402042Notes

Reaction equation

HRID 402042 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[C:19](Cl)[N:18]=[N:17][C:16]=2[CH2:22][CH2:23][CH2:24][CH3:25])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:26]([O:30][C:31]([N:33]1[CH2:38][CH2:37][CH:36]([NH2:39])[CH2:35][CH2:34]1)=[O:32])([CH3:29])([CH3:28])[CH3:27].C1CCN2C(=NCCC2)CC1.C1C[O:54][CH2:53]C1>>[C:26]([O:30][C:31]([N:33]1[CH2:38][CH2:37][CH:36]([NH:39][C:53]([C:19]2[N:18]=[N:17][C:16]([CH2:22][CH2:23][CH2:24][CH3:25])=[C:15]([C:12]3[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[CH:10][CH:11]=3)[CH:20]=2)=[O:54])[CH2:35][CH2:34]1)=[O:32])([CH3:29])([CH3:27])[CH3:28]

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 12682914-Amino-1-Boc-piperidineHCID 713030894-(4-(Benzyloxy)phenyl)-3-butyl-6-chloropyridazine

Product 1

HCID 67373952HCID 67373952, compound

Conditions

Temperature
150 °C

Procedure

A 5.0 mL vial was charged with 4-(4-benzyloxy-phenyl)-3-butyl-6-chloro-pyridazine (Example 1, 0.3 g, 0.85 mmol), 4-amino-piperidine-1-carboxylic acid tert-butyl ester (0.51 g, 2.5 mmol), Mo(CO)6 (0.22 g, 0.85 mmol), (trans-di-μ-acetobis[2-(di-o-tolylphosphino)benzyl]dipalladium(II) (0.08 g, 0.085 mmol) and THF (3.0 mL). DBU (0.16 g, 1.06 mmol) was added, and the vial was immediately sealed. The reaction mixture was then exposed to microwave heating for 15 min at a pre-selected maximum temperature of 150° C. The reaction was thereafter cooled to room temperature. The mixture was filtered through a small plug of celite, and the plug was washed with DCM. The combined fractions were evaporated under reduced pressure, and the crude product was purified by column chromatography (silica gel) eluting first with DCM and then 5% methanol in DCM. The combined fractions were evaporated and purified by column chromatography (silica gel) eluting with 30% ethyl acetate in hexane to get 4-{[5-(4-benzyloxy-phenyl)-6-butyl-pyridazine-3-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester (0.120 g). LCMS: m/z 546.4 [M+2].

Workup

  1. customthe vial was immediately sealed
  2. temperatureThe reaction was thereafter cooled to room temperature
  3. filtrationThe mixture was filtered through a small plug of celite
  4. washthe plug was washed with DCM
  5. customThe combined fractions were evaporated under reduced pressure
  6. customthe crude product was purified by column chromatography (silica gel)
  7. washeluting first with DCM
  8. customThe combined fractions were evaporated
  9. custompurified by column chromatography (silica gel)
  10. washeluting with 30% ethyl acetate in hexane

Sources & evidence

ORD record
ord-deda7cf973134ff788d6b1ebd04eb57a
Source dataset
uspto-grants-2014_06
Patent number
US08741900B2

Reaction notes

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