Sodium Carbonate → 1-[5-(2-Fluoro-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclobutanol

HRID 1039991Notes

Reaction equation

HRID 1039991 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][N:10]=2)=[CH:4][C:3]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[Na+].[Na+].Br[C:35]1[S:39][C:38]([C:40]2([OH:44])[CH2:43][CH2:42][CH2:41]2)=[N:37][CH:36]=1>CN(C=O)C.C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:16])([F:17])[F:18])[CH:12]=[CH:11][N:10]=2)=[CH:4][C:3]=1[C:35]1[S:39][C:38]([C:40]2([OH:44])[CH2:43][CH2:42][CH2:41]2)=[N:37][CH:36]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 58456224HCID 58456224, compoundHCID 67258663N-[4-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine

Product 1

HCID 584564151-[5-(2-Fluoro-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclobutanolYield 24.9%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of the product of Step 2 (383 mg, 1.0 mmol) in DMF (2 mL) and aqueous sodium carbonate (2 M, 1.5 mL, 3.0 mmol) in a microwave vial was added Intermediate 1 (234 mg, 1.0 mmol), and PdCl2(dppf)-dichloromethane adduct (82 mg, 0.1 mmol) under dry nitrogen. The vial was sealed and the reaction was heated in a microwave at 85° C. for 2 hours. The reaction was cooled to room temperature, diluted with ethyl acetate, washed with water, then brine and was dried over sodium sulfate. The organic was concentrated after filtration and was purified by flash chromatography (25:75 ethyl acetate:hexanes) to afford 1-[5-(2-fluoro-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclobutanol as an off-white foamy solid (102 mg, 0.249 mmol, 24.9%). 1H NMR (500 MHz, CDCl3): δ 8.66 (d, J=4.9 Hz, 1H); 8.07 (s, 1H); 8.03 (d, J=6.1 Hz, 1H); 7.82 (s, 1H); 7.50 (dt, J=8.8, 3.4 Hz, 1H); 7.16 (t, J=9.6 Hz, 1H); 7.07 (d, J=4.9 Hz, 1H); 4.07 (s, 1H); 2.77-2.70 (m, 2H); 2.59-2.49 (m, 2H); 2.13-1.98 (m, 2H). rhSYK activity=++

Workup

  1. customThe vial was sealed
  2. temperatureThe reaction was cooled to room temperature
  3. washwashed with water
  4. dry with materialbrine and was dried over sodium sulfate
  5. concentrationThe organic was concentrated
  6. filtrationafter filtration
  7. customwas purified by flash chromatography (25:75 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-a055fa6bcef24d7ba33a7aa53a2ae64a
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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