Potassium Phosphate, Tribasic → 6-Morpholino-5-(pyrimidin-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

HRID 923984Notes

Reaction equation

HRID 923984 reaction equation
Br[C:2]1[C:3]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].[N:28]1[CH:33]=[C:32](B(O)O)[CH:31]=[N:30][CH:29]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1>[O:25]1[CH2:26][CH2:27][N:22]([C:3]2[C:2]([C:32]3[CH:33]=[N:28][CH:29]=[N:30][CH:31]=3)=[CH:21][C:6]([C:7]([NH:9][C:10]3[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=3)=[O:8])=[CH:5][N:4]=2)[CH2:23][CH2:24]1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 899067015-Bromo-6-morpholino-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Product 1

HCID 899074486-Morpholino-5-(pyrimidin-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

5-Bromo-6-morpholino-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 148.1, 60 mg, 0.134 mmol), pyrimidin-5-ylboronic acid (50 mg, 0.403 mmol), Pd(Ph3P)4 (12.43 mg, 10.76 μmol) and finely ground K3PO4 (143 mg, 0.672 mmol) were added to a MW vial and treated with toluene (672 μL). The vial was sealed, evacuated/purged with argon then the RM was stirred 110° C. for 16 h, diluted with DME (2 mL), treated with Si-Thiol (Silicycle, 1.44 mmol/g, 56.0 mg, 0.081 mmol), centrifuged, the supernatant was filtered and the solvent was evaporated off under reduced pressure to give a residue which was purified by preparative SFC (Column Diol, from 15% to 20% in 6 min) to yield the title product as a white solid. UPLC-MS (Condition 3) tR=1.00 min, m/z=446.3 [M+H]+, m/z=444.1 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 3.09-3.20 (m, 4H) 3.50-3.60 (m, 4H) 7.38 (d, J=8.28 Hz, 2H) 7.86 (d, J=9.16 Hz, 2H) 8.23 (d, J=2.38 Hz, 1H) 8.84 (d, J=2.38 Hz, 1H) 9.13 (s, 2H) 9.22 (s, 1H) 10.37 (s, 1H).

Workup

  1. customThe vial was sealed
  2. customevacuated/purged with argon
  3. additiondiluted with DME (2 mL)
  4. filtrationthe supernatant was filtered
  5. customthe solvent was evaporated off under reduced pressure
  6. customto give a residue which
  7. customwas purified by preparative SFC (Column Diol, from 15% to 20% in 6 min)

Sources & evidence

ORD record
ord-6d9b3b828c6349129a4b046c021e5a5a
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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