Cesium carbonate → 7-(3-(trifluoromethyl)pyridin-2-yl)-N-(5-(trifluoromethyl)pyridin-2-yl)-1,8-naphthyridin-4-amine

HRID 1724880Notes

Reaction equation

HRID 1724880 reaction equation
Cl[C:2]1[CH:11]=[CH:10][N:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([C:12]1[C:17]([C:18]([F:21])([F:20])[F:19])=[CH:16][CH:15]=[CH:14][N:13]=1)=[N:7]2.[NH2:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][N:24]=1.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.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.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]>[F:19][C:18]([F:21])([F:20])[C:17]1[C:12]([C:6]2[N:7]=[C:8]3[C:3]([C:2]([NH:22][C:23]4[CH:28]=[CH:27][C:26]([C:29]([F:31])([F:30])[F:32])=[CH:25][N:24]=4)=[CH:11][CH:10]=[N:9]3)=[CH:4][CH:5]=2)=[N:13][CH:14]=[CH:15][CH:16]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 7358622-Amino-5-(trifluoromethyl)pyridineHCID 462035425-Chloro-2-(3-(trifluoromethyl)pyridin-2-yl)-[1,8]naphthyridine

Product 1

HCID 462038647-(3-(trifluoromethyl)pyridin-2-yl)-N-(5-(trifluoromethyl)pyridin-2-yl)-1,8-naphthyridin-4-amine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

Heat a mixture of 5-chloro-2-(3-(trifluoromethyl)pyridin-2-yl)-[1,8]naphthyridine (62 mg, 0.2 mmol), 2-amino-5-trifluoromethylpyridine (32.4 mg, 0.2 mmol), xantphos (11.6 mg, 0.02 mmol), Pd2(dba)3 (18.3 mg, 0.02 mmol) and Cs2CO3 (130 mg, 0.4 mmol) in dioxane (2.0 mL) at 100° C. for 20 hours. Cool the mixture, concentrate under vacuum, dilute with EtOAc/water (5.0 mL each), filter through celite, wash celite with EtOAc (2×5 mL) and dry combined organic layers with MgSO4. Filter the dried extract and concentrate under vacuum to afford crude product. Purify by preparative TLC using EtOAc as eluent to afford title compound as a yellow solid. 1H NMR (400 MHZ, DMSO-D6) δ 10.15 (s, 1H), 9.1 (d, 1H, J=2.2 Hz), 9.0 (d, 1H, J=1.1 Hz), 8.95 (d, 1H, J=1.2 Hz), 8.68 (s, 1H), 8.50 (d, 1H, J=1.3 Hz), 8.43 (d, 1H, J=2.0 Hz), 8.12 (dd, 1H), 8.0(d, 1H, J=2.2 Hz), 7.81 (m, 1H), 7.49 (d, 1H, J=2.2 Hz). MS=436.08 (M+H).

Workup

  1. temperatureHeat
  2. temperatureCool the mixture
  3. concentrationconcentrate under vacuum
  4. additiondilute with EtOAc/water (5.0 mL each)
  5. filtrationfilter through celite
  6. washwash celite with EtOAc (2×5 mL)
  7. customdry
  8. filtrationFilter the dried
  9. extractionextract
  10. concentrationconcentrate under vacuum
  11. customto afford crude product
  12. customPurify by preparative TLC

Sources & evidence

ORD record
ord-6e717f08228b48eba707164519683d7e
Source dataset
uspto-grants-2009_02
Patent number
US07488740B2

Reaction notes

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