Potassium Phosphate, Tribasic → HCID 86689241, compound

HRID 1409506Notes

Reaction equation

HRID 1409506 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].Cl[C:9]1[N:14]=[C:13]([F:15])[C:12]2[O:16][C:17]3[C:22]([C:23]4([C:31]5[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=5)[C:25]([NH2:32])=[N:24]4)[C:11]=2[CH:10]=1)=[CH:21][C:20]([C:33]1[C:34]([F:39])=[N:35][CH:36]=[CH:37][CH:38]=1)=[CH:19][CH:18]=3.[F:40][C:41]1[CH:46]=[C:45](B(O)O)[CH:44]=[CH:43][N:42]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[F:15][C:13]1[C:12]2[O:16][C:17]3[C:22]([C:23]4([C:31]5[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=5)[C:25]([NH2:32])=[N:24]4)[C:11]=2[CH:10]=[C:9]([C:45]2[CH:44]=[CH:43][N:42]=[C:41]([F:40])[CH:46]=2)[N:14]=1)=[CH:21][C:20]([C:33]1[C:34]([F:39])=[N:35][CH:36]=[CH:37][CH:38]=1)=[CH:19][CH:18]=3

Participants

4

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27833962-Fluoropyridine-4-boronic acidHCID 86689242HCID 86689242, compound

Product 1

HCID 86689241HCID 86689241, compoundYield 48.3%

Conditions

Temperature
100 °C

Procedure

A microwave vial was charged with 3-chloro-1-fluoro-7-(2-fluoropyridin-3-yl)spiro[chromeno[2,3-c]pyridine-5,1′-isoindol]-3′-amine 2,2,2-trifluoroacetate (43 mg, 0.077 mmol, step 3), 2-fluoropyridine-4-boronic acid (27.0 mg, 0.192 mmol, Aldrich), bis[di-tert-butyl(4-dimethylaminophenyl)phosphine]dichloropalladium(II) (5.43 mg, 7.67 μmol, Aldrich) and potassium phosphate (48.8 mg, 0.230 mmol, Aldrich). The vial was evacuated and backfilled with N2 gas (2×). Dioxane (0.6 mL) and water (0.2 mL) were added, and the vial was heated in the microwave for 30 min at 100° C. The reaction mixture was partitioned between EtOAc and water. The organic phase was separated and the solvent was removed under reduced pressure. The residue was purified by reversed-phase preparative HPLC using a Phenomenex Gemini column, 10 micron, C18, 110 Å, 100×50 mm, 0.1% TFA in CH3CN/H2O, gradient 10% to 100% over 20 min to obtain the title product (23 mg, 0.037 mmol, 48.3% yield) as a light-yellow solid. MS m/z=508.1 [M+H]+. Calculated for C29H16F3N5OC2HF3O2: 621.49 (TFA salt). 1H-NMR (300 MHz, MeOH) δ ppm 7.14 (t, J=1.61 Hz, 1H) 7.30-7.39 (m, 1H) 7.39-7.48 (m, 1H) 7.53-7.70 (m, 3H) 7.72-7.86 (m, 4H) 7.92 (ddd, J=9.94, 7.75, 1.90 Hz, 1H) 8.16 (d, J=4.97 Hz, 1H) 8.22 (d, J=5.41 Hz, 1H) 8.26-8.37 (m, 1H).

Workup

  1. customThe vial was evacuated
  2. additionDioxane (0.6 mL) and water (0.2 mL) were added
  3. customThe reaction mixture was partitioned between EtOAc and water
  4. customThe organic phase was separated
  5. customthe solvent was removed under reduced pressure
  6. customThe residue was purified by reversed-phase preparative HPLC
  7. customover 20 min

Sources & evidence

ORD record
ord-bc62cf683e1940708635a9963dff3e70
Source dataset
uspto-grants-2014_12
Patent number
US08921363B2

Reaction notes

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