Thiophene-3-boronic acid → HCID 59375391, compound

HRID 2192976Notes

Reaction equation

HRID 2192976 reaction equation
Br[C:2]1[C:11]2[N:10]=[C:9]([NH:12][C@H:13]([CH3:17])[CH:14]([CH3:16])[CH3:15])[C:8]3[CH:18]=[CH:19][C:20]([F:22])=[CH:21][C:7]=3[C:6]=2[C:5](=[O:23])[NH:4][CH:3]=1.[S:24]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25]1>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+]>[CH3:17][C@@H:13]([NH:12][C:9]1[C:8]2[CH:18]=[CH:19][C:20]([F:22])=[CH:21][C:7]=2[C:6]2[C:5](=[O:23])[NH:4][CH:3]=[C:2]([C:26]3[CH:27]=[CH:28][S:24][CH:25]=3)[C:11]=2[N:10]=1)[CH:14]([CH3:16])[CH3:15]

Participants

5

Reactant 2

HCID 581760Thiophene-3-boronic acidHCID 59375579HCID 59375579, compound

Product 1

HCID 59375391HCID 59375391, compound

Reagents, catalysts & solvents 2

HCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 4-bromo-6-{[(1R)-1,2-dimethylpropyl]amino}-9-fluorobenzo[c]-1,6-naphthyridin-1(2H)-one (32 mg, 0.085 mmol) in dioxane (2 mL) and Na2CO3 (1 mL, 2.0 M) were added 3-thienylboronic acid (13 mg, 0.10 mmol) and palladium tetrakistriphenylphosphine (24 mg, 0.021 mmol). The solution was degassed by bubbling nitrogen gas and heated in a microwave reactor at 150° C. for 1 hr. The resulting solution was filtered and purified by reverse phase HPLC to produce 6-{[(1R)-1,2-dimethylpropyl]amino}-9-fluoro-4-(3-thienyl)benzo[c]-1,6-naphthyridin-1(2H)-one. 1H NMR (600 MHz, CD3OD) δ 9.63 (dd, 1H), 8.40 (m, 1H), 7.68 (m, 1H), 7.57 (s, 1H), 7.50 (m, 1H), 7.46 (d, 1H), 7.40 (m, 1H), 4.20 (br s, 1H), 1.98 (m, 1H), 1.24 (d, 3H), 0.93 (m, 6H). LRMS (ESI) calc'd for (C21H21FN3OS) [M+H]+, 382.1; found 382.1.

Workup

  1. customThe solution was degassed
  2. customby bubbling nitrogen gas
  3. filtrationThe resulting solution was filtered
  4. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-82266223b4ad4211abdc99bdcfb1612b
Source dataset
uspto-grants-2012_12
Patent number
US08329722B2

Reaction notes

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