Triethylamine → HCID 178434460, compound

HRID 2241324Notes

Reaction equation

HRID 2241324 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13](=[O:14])[C:12]([C:15]([OH:17])=O)=[CH:11][CH:10]=[N:9]2)=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.COC1C=CC(C[N:31]2[C:35]3=[N:36][CH:37]=[CH:38][C:39]([O:40][C:41]4[C:46]([F:47])=[CH:45][C:44]([NH2:48])=[C:43]([F:49])[CH:42]=4)=[C:34]3[C:33]([CH3:50])=[N:32]2)=CC=1.C(N(CC)CC)C>CN(C=O)C.CN(C)C1C=CN=CC=1.O.C(Cl)Cl>[F:49][C:43]1[CH:42]=[C:41]([O:40][C:39]2[CH:38]=[CH:37][N:36]=[C:35]3[NH:31][N:32]=[C:33]([CH3:50])[C:34]=23)[C:46]([F:47])=[CH:45][C:44]=1[NH:48][C:15]([C:12]1[C:13](=[O:14])[N:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[N:9]=[CH:10][CH:11]=1)=[O:17]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 667671712-(4-Fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxylic acidHCID 68514955HCID 68514955, compound

Product 1

HCID 178434460HCID 178434460, compoundYield 211.8%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
70 °C

Procedure

Charge a 100 mL round-bottomed flask with 2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxylic acid (0.103 g, 0.442 mmol obtained from Example 19, step C), and CH2Cl2 (10 mL). Oxalyl chloride in DCM (2M) (2.84 ml, 5.68 mmol) and DMF (3 drops) were added. The reaction mixture was stirred for 1 hour and concentrated. The crude material was resuspend in DCM and 4-(1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-2,5-difluorobenzenamine (0.750 g, 1.89 mmol), N,N-dimethylpyridin-4-amine (0.0231 g, 0.189 mmol) and triethylamine (0.287 g, 2.84 mmol) were added. The reaction mixture was stirred at r ambient temperature for 16 hours, then diluted with water and DCM. The organic layer washed with brine, dried over sodium sulfate, filtered and concentrated. The crude material was purified by chromatography, eluting with EtOAc and concentrated. To the crude material in a 25 mL RBF was add TFA (3 mL). The mixture was heated to 70° C. for 2 hours, then cooled to ambient temperature and concentrated. The residue was triturated with DCM/MeOH 1:1 (5 mL) to afford 461 mg (46%) of the desired product. LRMS M+1 (493.1) observed. 1H NMR (400 MHz, DMSOd6) δ12.14 (s, 1H), 8.54 (s, 1H), 8.43 (m, 1H), 8.36 (m, 1H), 8.30 (m, 1H), 7.77 (m, 1H), 7.68 (m, 2H), 7.42 (t, J=8 Hz, 2H), 6.35 (d, J=5 Hz, 1H), 2.62 (s, 3H).

Workup

  1. concentrationconcentrated
  2. stirringThe reaction mixture was stirred at r ambient temperature for 16 hours
  3. washThe organic layer washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by chromatography
  8. washeluting with EtOAc
  9. concentrationconcentrated
  10. additionTo the crude material in a 25 mL RBF was add TFA (3 mL)
  11. temperaturecooled to ambient temperature
  12. concentrationconcentrated
  13. customThe residue was triturated with DCM/MeOH 1:1 (5 mL)

Sources & evidence

ORD record
ord-c917bb2dc0c2453fbf0b0e66b09ab7ff
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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