3,6-Dibromopyridazine → HCID 86686650, compound

HRID 627404Notes

Reaction equation

HRID 627404 reaction equation
Br[C:2]1[N:3]=[N:4][C:5](Br)=[CH:6][CH:7]=1.[C:9]([O:13][C:14]([N:16]1[CH:22]2[CH2:23][CH2:24][CH:17]1[CH2:18][NH:19][C:20](=[O:25])[CH2:21]2)=[O:15])([CH3:12])([CH3:11])[CH3:10].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CC([O-])(C)C.[Na+].[CH3:74][N:75]([CH3:93])[C:76]([C:78]1[N:87]([CH:88]2[CH2:92][CH2:91][CH2:90][CH2:89]2)[C:81]2[N:82]=[C:83]([NH2:86])[N:84]=[CH:85][C:80]=2[CH:79]=1)=[O:77]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:9]([O:13][C:14]([N:16]1[CH:22]2[CH2:23][CH2:24][CH:17]1[CH2:18][N:19]([C:2]1[N:3]=[N:4][C:5]([NH:86][C:83]3[N:84]=[CH:85][C:80]4[CH:79]=[C:78]([C:76](=[O:77])[N:75]([CH3:74])[CH3:93])[N:87]([CH:88]5[CH2:92][CH2:91][CH2:90][CH2:89]5)[C:81]=4[N:82]=3)=[CH:6][CH:7]=1)[C:20](=[O:25])[CH2:21]2)=[O:15])([CH3:12])([CH3:10])[CH3:11]

Participants

8

Reactant 5

HCID 2488523,6-DibromopyridazineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)2×HCID 23676156Sodium t-butoxide2×HCID 585748429-Boc-4-oxo-3,9-diaza-bicyclo[4.2.1]nonaneHCID 673553691331847-17-6

Product 1

HCID 86686650HCID 86686650, compoundYield 24.7%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of 3,6-dibromo-pyridazine (400 mg, 1.68 mmol) in 8 mL Toluene in a dry pressure tube were added 4-oxo-3,9-diaza-bicyclo[4.2.1]nonane-9-carbo-xylic acid tert-butyl ester (323 mg, 1.345 mmol), Pd2(dba)3 (154 mg, 0.168 mmol), xantphos (195 mg, 0.336 mmol) and NaOt-Bu (242 mg, 2.52 mmol) and the suspension was bubbled with N2 for 3 min. Then the tube was sealed and the mixture was heated for 3 h at 100° C. Then the seal was open and the mixture was added with more of Pd2(dba)3 (41 mg, 0.045 mmol), xantphos (52 mg, 0.091 mmol), NaOt-Bu (65 mg, 0.680 mmol) and 2-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (124 mg, 0.453 mmol). The mixture was again heated at 100 C for 16 h and the suspension was filtered through a celite plug and washed with 10% MeOH in DCM. The collective filtrates were combined and purified by two consecutive SiO2 columns to give 3-[6-(7-cyclopentyl-6-dimethylcarbamoyl-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)pyridazin-3-yl]-4-oxo-3,9-diaza-bicyclo[4.2.1]nonane-9-carboxylic acid tert-butyl ester (66 mg, 0.112 mmol, 8% yield) as a white solid. MS m/z 590.6 (M+H)+.

Workup

  1. customthe suspension was bubbled with N2 for 3 min
  2. customThen the tube was sealed
  3. temperatureThe mixture was again heated at 100 C for 16 h
  4. filtrationthe suspension was filtered through a celite plug
  5. washwashed with 10% MeOH in DCM
  6. custompurified by two consecutive SiO2 columns

Sources & evidence

ORD record
ord-78e3ca50bf3f48fdbd459d35baf96100
Source dataset
uspto-grants-2016_04
Patent number
US09309252B2

Reaction notes

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