Potassium Phosphate, Tribasic → HCID 90077314, compound

HRID 1050261Notes

Reaction equation

HRID 1050261 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[NH:25][C:24]([O:26][C@H:27]3[CH2:32][O:31][C@H:30]([CH2:33][OH:34])[C@@H:29]([OH:35])[CH2:28]3)=[N:23][C:5]2=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11](B2OC(C)(C)C(C)(C)O2)=[CH:10][CH:9]=1.Br[C:37]1[CH:42]=[CH:41][C:40]([CH:43]([NH2:48])[C:44]([F:47])([F:46])[F:45])=[CH:39][CH:38]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>>[NH2:48][CH:43]([C:40]1[CH:41]=[CH:42][C:37]([C:11]2[CH:10]=[CH:9][C:8]([C:7]3[N:6]=[C:5]4[N:23]=[C:24]([O:26][C@H:27]5[CH2:32][O:31][C@H:30]([CH2:33][OH:34])[C@@H:29]([OH:35])[CH2:28]5)[NH:25][C:4]4=[CH:3][C:2]=3[Cl:1])=[CH:13][CH:12]=2)=[CH:38][CH:39]=1)[C:44]([F:45])([F:46])[F:47]

Participants

4

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 121647401-(4-Bromophenyl)-2,2,2-trifluoroethanamineHCID 90043210HCID 90043210, compound

Product 1

HCID 90077314HCID 90077314, compound

Conditions

Temperature
80 °C

Procedure

A 10 mL reaction vial was charged with (2R,3S,5R)-5-((6-chloro-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazo[4,5-b]pyridin-2-yl)oxy)-2-(hydroxymethyl)-tetrahydro-2H-pyran-3-ol (61.2 mg, 0.122 mmol), 1-(4-bromophenyl)-2,2,2-trifluoroethanamine (35 mg, 0.102 mmol), potassium phosphate tribasic (108 mg, 0.509 mmol), and [1,1′-[1,1′-Bis(Diphenyl-phosphino)-Ferrocene]Dichloropalladium (II) (14.89 mg, 0.020 mmol). The reaction vessel was evacuated and backfilled with N2 (×3), and degassed dioxane (339 μl) and water (339 μl) were added. The reaction was heated to 80° C. for 4 h, then diluted with water and EtOAc. The aqueous phase was extracted with EtOAc (×2); and the combined extracts were washed with brine, dried over Na2SO4, filtered, and concentrated. The resulting residue was purified by mass directed reverse phase HPLC eluted with acetonitrile in water containing 0.1% formic acid. The desired fractions were combined and lyophilized to give the title compound as a white solid. LC-MS: calculated for C26H24ClF3N4O4 548.14 observed m/e: 549.14 (M+H)+ (Rt 1.55/4 min); 1H NMR δ (ppm) (CD3OD): 7.90 (d, 1H), 7.84 (s, 1H), 7.78 (s, 4H), 7.67 (d, 2H), 5.42 (q, 1H), 5.12 (septet, 1H), 4.35 (dd, 1H), 3.88 (d, 1H), 3.66-3.59 (m, 2H), 3.37 (t, 1H), 3.18-3.15 (m, 1H), 2.76-2.74 (m, 1H), 1.69 (q, 1H).

Workup

  1. customA 10 mL reaction
  2. customThe reaction vessel was evacuated
  3. customdegassed dioxane (339 μl) and water (339 μl)
  4. additionwere added
  5. additiondiluted with water and EtOAc
  6. extractionThe aqueous phase was extracted with EtOAc (×2)
  7. washand the combined extracts were washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe resulting residue was purified by mass
  12. washeluted with acetonitrile in water containing 0.1% formic acid

Sources & evidence

ORD record
ord-730301b21de84248ba738b6b4cad8208
Source dataset
uspto-grants-2016_07
Patent number
US09382243B2

Reaction notes

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