Sodium Carbonate → HCID 89907351, compound

HRID 923843Notes

Reaction equation

HRID 923843 reaction equation
Br[C:2]1[C:3](Cl)=[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].[NH:23]1[CH2:27][CH2:26][CH:25]([OH:28])[CH2:24]1.CCN(C(C)C)C(C)C.[N:38]1[CH:43]=[C:42](B(O)O)[CH:41]=[N:40][CH:39]=1.C([O-])([O-])=O.[Na+].[Na+]>CC(O)C.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>[OH:28][CH:25]1[CH2:26][CH2:27][N:23]([C:3]2[C:2]([C:42]3[CH:43]=[N:38][CH:39]=[N:40][CH:41]=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)[CH2:24]1

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 982104-HydroxypyrrolidineHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 867025955-bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Product 1

HCID 89907351HCID 89907351, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 3776IsopropanolSolvent

Procedure

5-Bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 12.2, 60 mg, 0.152 mmol), (Rac.)-pyrrolidin-3-ol (15.86 mg, 0.182 mmol), and DIPEA (53.0 μL, 0.303 mmol) in iPrOH (250 μL) were added to a MW vial and subjected to MW irradiation at 110° C. for 20 min. The RM was then transferred into a MV vial containing pyrimidin-5-ylboronic acid (56.4 mg, 0.455 mmol), Pd(PPh3)2Cl2 (10.65 mg, 0.015 mmol), Na2CO3 (80 mg, 0.758 mmol) and treated with a mixture of DME (600 μL)-water (200 μL). The vial was sealed, evacuated/purged with argon and the RM was subjected to MW irradiation at 80° C. for 2 h. The RM was cooled to RT, diluted with THF (1.5 mL), treated with Si-Thiol (Silicycle, 59.7 mg, 0.076 mmol), filtered and the filtrate was evaporated off under reduced pressure to give a residue which was purified by preparative HPLC (Condition 13, 30% for 0.2 min then 30% to 60% in 12 min) to yield the title compound as a white solid. UPLC-MS (condition 1) tR=2.01 min, m/z=446.0 [M+H]+, m/z=444.1 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.70-1.79 (m, 1H) 1.79-1.90 (m, 1H) 2.88 (d, J=11.0 Hz, 1H) 3.18-3.27 (m, 2H) 3.38-3.43 (m, 1H) 4.17-4.25 (m, 1H) 4.79-5.01 (m, 1H) 7.35 (d, J=8.3 Hz, 2H) 7.85 (d, J=4.9 Hz, 2H) 8.10 (d, J=2.4 Hz, 1H) 8.79 (d, J=2.4 Hz, 1H) 8.89 (s, 2H) 9.19 (s, 1H) 10.18 (s, 1H).

Workup

  1. customsubjected to MW irradiation at 110° C. for 20 min
  2. customThe vial was sealed
  3. customevacuated/purged with argon
  4. customthe RM was subjected to MW irradiation at 80° C. for 2 h
  5. additiondiluted with THF (1.5 mL)
  6. filtrationfiltered
  7. customthe filtrate was evaporated off under reduced pressure
  8. customto give a residue which
  9. customwas purified by preparative HPLC (Condition 13, 30% for 0.2 min

Sources & evidence

ORD record
ord-3813dc17bf694f2681e134eac1badfca
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

Loading…