Sodium Bicarbonate → HCID 72203421, compound

HRID 629080Notes

Reaction equation

HRID 629080 reaction equation
Br[C:2]1[C:3]([C:22]2[CH2:23][CH2:24][O:25][CH2:26][CH:27]=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.C([O-])(O)=O.[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.COCCOC>[O:25]1[CH2:26][CH:27]=[C: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 516892Sodium BicarbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 89906637HCID 89906637, compound

Product 1

HCID 72203421HCID 72203421, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

5-Bromo-6-(3,6-dihydro-2h-pyran-4-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 44.1, 160 mg, 0.361 mmol), pyrimidin-5-ylboronic acid (89 mg, 0.722 mmol), Pd(PPh3)2Cl2 (25 mg, 0.036 mmol), aq. 2 M NaHCO3 (0.541 mL, 1 mmol) and DME (1.5 mL) were added to a vial, which was sealed, evacuated/purged with argon and the RM was stirred at 90° C. for 1.5 h. The RM was diluted with EtOAc, washed with brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give the crude product which was purified by flash chromatography (RediSep® Silica gel column, DCM/MeOH from 2 to 5% MeOH) and treated with Si-Thiol (90 mg) in MeOH to afford the title product as a solid. HPLC (Condition 3) tR=4.99 min, UPLC-MS (Condition 2) m/z=443.2 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 2.39-2.60 (m, 2H) 3.74 (t, J=5.47 Hz, 2H) 3.90-4.00 (m, 2H) 5.58 (s, 1H) 7.39 (d, J=8.99 Hz, 2H) 7.77-7.92 (m, 2H) 8.40 (d, J=1.96 Hz, 1H) 8.94 (s, 2H) 9.12 (d, J=1.00 Hz, 1H) 9.21 (s, 1H) 10.60 (s, 1H).

Workup

  1. customwas sealed
  2. customevacuated/purged with argon
  3. additionThe RM was diluted with EtOAc
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. customthe solvent was evaporated off under reduced pressure
  7. customto give the crude product which
  8. customwas purified by flash chromatography (RediSep® Silica gel column, DCM/MeOH from 2 to 5% MeOH)
  9. additiontreated with Si-Thiol (90 mg) in MeOH

Sources & evidence

ORD record
ord-688c1c7ec06d492caaf0a7c4edba8e1d
Source dataset
uspto-grants-2016_04
Patent number
US09315489B2

Reaction notes

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