Sodium Carbonate → HCID 58529515, compound

HRID 1972886Notes

Reaction equation

HRID 1972886 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([C:13]([C:15]2[N:23]3[C:18]([C:19]([NH2:24])=[N:20][CH:21]=[N:22]3)=[C:17](Br)[CH:16]=2)=[O:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:26]([N:33]1[CH:41]=[C:40]2[C:35]([CH:36]=[C:37](B3OC(C)(C)C(C)(C)O3)[CH:38]=[CH:39]2)=[N:34]1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([C:13]([C:15]2[N:23]3[C:18]([C:19]([NH2:24])=[N:20][CH:21]=[N:22]3)=[C:17]([C:37]3[CH:38]=[CH:39][C:40]4[C:35]([CH:36]=3)=[N:34][N:33]([CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH:41]=4)[CH:16]=2)=[O:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 585293132-benzyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-IndazoleHCID 58529901HCID 58529901, compound

Product 1

HCID 58529515HCID 58529515, compoundYield 66.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

To a stirred solution 3-(4-amino-5-bromo-pyrrolo[2,1-f][1,2,4]triazine-7-carbonyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (1.33 g, 3.24 mmol), intermediate C (1.63 g, 4.86 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.37 g, 0.32 mmol) in degassed DMF (35 mL) was added aqueous Na2CO3 (2M, 5.34 mL). The resulting mixture was heated at 110° C. for 3 h and then cooled to rt. The reaction mixture was diluted with EtOAc and filtered through a Celite® pad. The organic layer was separated and concentrated in vacuo. The residue was purified by silica-gel column using a gradient of 50 to 100% EtOAc in hexanes to afford 1.16 g (66%) of the desired product. 1H-NMR (CD3OD-d4) 8.39 (s, 1H), 8.05 (s, 1H), 7.87 (dd, 1H), 7.70 (s, 1H), 7.50 (s, 1H), 7.37-7.29, (m, 5 H), 7.24 (dd, 1 H), 5.67 (s, 1 H), 4.47-4.39 (m, 2 H), 3.71-3.59 (m, 2 H), 2.34-2.12 (m, 2 H), 1.45 (s, 1H); LC-MS [M+H]+=537.9, RT=3.36 min.

Workup

  1. temperaturecooled to rt
  2. filtrationfiltered through a Celite® pad
  3. customThe organic layer was separated
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica-gel column

Sources & evidence

ORD record
ord-d0fbb096ffa849f3821201b278c73528
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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