Ethyl Acetate → HCID 59380399, compound

HRID 2353852Notes

Reaction equation

HRID 2353852 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]2[C:8]3[C:13]([NH:14][C:15]4[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=5)=[C:17]([Cl:29])[CH:16]=4)=[N:12][CH:11]=[N:10][C:9]=3[S:30][C:4]=2[CH:3]=1.[K].C(=O)([O-])[O-].[Na+].[Na+].[CH3:38][CH2:39]OC(C)=O>COCCOC.O.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>[Cl:29][C:17]1[CH:16]=[C:15]([NH:14][C:13]2[C:8]3[C:5]4[CH:6]=[CH:7][C:2]([CH:38]=[CH2:39])=[CH:3][C:4]=4[S:30][C:9]=3[N:10]=[CH:11][N:12]=2)[CH:20]=[CH:19][C:18]=1[O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 5462222PotassiumHCID 59380449HCID 59380449, compound

Product 1

HCID 59380399HCID 59380399, compoundYield 97%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of 7-bromo-N-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl][1]benzothieno[2,3-d]pyrimidin-4-amine (5.0 g, 10.0 mmol) in 1,2-dimethoxyethane (50 mL) and water (5.0 mL) were added Pd(PPh3)4 (580 mg, 0.50 mmol, 0.05 equiv), Potassium vinyltrifluoroorate (1.48 g, 11.1 mmol, 1.1 equiv), and sodium carbonate (2.66 g, 25.1 mmol, 2.5 equiv) under nitrogen. The reaction mixture was heated to reflux for 15 hours. The reaction mixture was cooled to rt then poured into a flask contains a mixture of water (100 mL) and EtOAc (100 mL). The resulting mixture was extracted with EtOAc (3×50 mL), dried over sodium sulfate then concentrated in vacuo. The crude material was purified by chromatography (5% EtOAc/hexane) to give an off-white solid (4.84 g, 97%). 1H-NMR (CD3OD) δ 8.72 (d, J=5.4 Hz, 1H), 8.47 (s, 1H), 8.37 (d, J=8.4 Hz, 1H), 8.28 (t, 1H), 8.06 (s, 1H), 7.98 (d, J=7.4 Hz, 1H), 7.81 (d, J=2.7 Hz, 1H), 7.72 (m, 2H), 7.55 (dd, J=2.1, 8.9 Hz, 1H), 7.23 (d, J=8.7 Hz, 1H), 6.89 (m, 1H), 5.97 (d, J=17.6 Hz, 1H), 5.43 (s, 2H), 5.39 (d, J=10.9 Hz, 1H); LCMS RT=3.30 min, [M+H]+=445.10.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 15 hours
  3. additionthen poured into a flask
  4. extractionThe resulting mixture was extracted with EtOAc (3×50 mL)
  5. dry with materialdried over sodium sulfate
  6. concentrationthen concentrated in vacuo
  7. customThe crude material was purified by chromatography (5% EtOAc/hexane)

Sources & evidence

ORD record
ord-a261779ca3cc48779b8e31c683f1b622
Source dataset
uspto-grants-2010_07
Patent number
US07750017B2

Reaction notes

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