Carbonic Acid → N-(4-(3-(3,6-Dihydro-2H-pyran-4-YL)pyridin-2-yloxy)phenyl)benzo[D]oxazol-2-amine

HRID 1880087Notes

Reaction equation

HRID 1880087 reaction equation
Br[C:2]1[C:3]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]3[O:17][C:18]4[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=4[N:20]=3)=[CH:11][CH:10]=2)=[N:4][CH:5]=[CH:6][CH:7]=1.[O:25]1[CH2:30][CH:29]=[C:28](B2OC(C)(C)C(C)(C)O2)[CH2:27][CH2:26]1.C(O)(O)=O.COCCOC>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.CCO.O>[O:25]1[CH2:26][CH:27]=[C:28]([C:2]2[C:3]([O:8][C:9]3[CH:14]=[CH:13][C:12]([NH:15][C:16]4[O:17][C:18]5[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=5[N:20]=4)=[CH:11][CH:10]=3)=[N:4][CH:5]=[CH:6][CH:7]=2)[CH2:29][CH2:30]1

Participants

8

Reactant 4

HCID 767Carbonic AcidHCID 80711,2-DimethoxyethaneHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 59327040N-(4-(3-Bromopyridin-2-yloxy)phenyl)benzo[D]oxazol-2-amine

Product 1

HCID 59327146N-(4-(3-(3,6-Dihydro-2H-pyran-4-YL)pyridin-2-yloxy)phenyl)benzo[D]oxazol-2-amine

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
140 °C

Procedure

A glass microwave reaction vessel was charged with N-(4-(3-bromopyridin-2-yloxy)phenyl)benzo[d]oxazol-2-amine (0.500 g, 1.308 mmol), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.414 g, 1.971 mmol), sodium carbonate anhydrous (0.700 g, 6.60 mmol) and trans-dichlorobis(triphenyl-phosphine)palladium (II) (0.092 g, 0.131 mmol, Strem). A mixture of 7:3:2 DME:H2O:EtOH (11 mL) was added and the reaction mixture was sealed under argon and heated in a Emrys Optmizer microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 140° C. for 15 min. The reaction mixture was partitioned between EtOAc/water and the aqueous layer was extracted with EtOAc (3×). The combined organic layers were evaporated onto silica gel and purified by flash chromatography (Isco (80 gram)) eluting with EtOAc:hexanes (0:1→1:2) to give a light-orange amorphous solid. MS (ESI, pos. ion) m/z: 386.0 (M+1). IC50 (uM) +++++.

Workup

  1. customA glass microwave reaction vessel
  2. customthe reaction mixture was sealed under argon
  3. customThe reaction mixture was partitioned between EtOAc/water
  4. extractionthe aqueous layer was extracted with EtOAc (3×)
  5. customThe combined organic layers were evaporated onto silica gel
  6. custompurified by flash chromatography (Isco (80 gram))
  7. washeluting with EtOAc:hexanes (0:1→1:2)
  8. customto give a light-orange amorphous solid

Sources & evidence

ORD record
ord-fc9de7c5b0ad442fb45b0daea4e9d272
Source dataset
uspto-grants-2012_11
Patent number
US08318718B2

Reaction notes

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