1,2-Dimethoxyethane → HCID 57635994, compound

HRID 216273Notes

Reaction equation

HRID 216273 reaction equation
Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[N:5]=[C:4]([NH:10][CH2:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=2[Cl:20])[CH:3]=1.[Cl:21][C:22]1[CH:27]=[CH:26][C:25](B2OC(C)(C)C(C)(C)O2)=[CH:24][C:23]=1[C:37]([OH:40])([CH3:39])[CH3:38].C([O-])([O-])=O.[Cs+].[Cs+].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:21][C:22]1[CH:27]=[CH:26][C:25]([C:2]2[CH:3]=[C:4]([NH:10][CH2:11][CH2:12][C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=3[Cl:20])[N:5]=[C:6]([O:8][CH3:9])[N:7]=2)=[CH:24][C:23]=1[C:37]([OH:40])([CH3:38])[CH3:39]

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10796Cesium carbonateHCID 576360046-Chloro-N-[2-(2,4-dichlorophenyl)ethyl]-2-methoxy-4-pyrimidinamineHCID 690687002-Chloro-α,α-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenemethanol

Product 1

HCID 57635994HCID 57635994, compoundYield 19.9%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×

Procedure

A solution of (6-chloro-2-methoxy-pyrimidin-4-yl)-[2-(2,4-dichlorophenyl)ethyl]amine (0.58 g), 2-[2-chloro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propan-2-ol (0.63 g), Cs2CO3 (1.36 g) and tetrakis(triphenylphosphine)palladium (0) (50 mg) in water (8 mL)/DME (32 mL) is heated at 90° C. for 16 h. The solution is poured into water and extracted with EtOAc (2×200 mL). The organic layer is dried over sodium sulfate, filtered, evaporated in vacuo. The residue is chromatographed on silica gel eluting with EtOAc to afford 2-(2-chloro-5-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-propan-2-ol (162 mg, Example 98). MS: 466 (M+H); 1H NMR (300 MHz, DMSO) □8.2 (m, 1H); 7.8, (d, 1H, J=0.3 Hz); 7.5-7.7 (m, 2H); 7.4 (d, 2H, J=0.4 Hz); 7.3 (m, 1H); 7.3 (s, 1H); 6.6 (s, 1H) 4.2 (s, 3H); 4 (s, 3H); 3.8 (m, 2H); 3.05 (t, 2H); 1.55 (s, 6H). IC50=110 nM

Workup

  1. extractionextracted with EtOAc (2×200 mL)
  2. dry with materialThe organic layer is dried over sodium sulfate
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. customThe residue is chromatographed on silica gel eluting with EtOAc

Sources & evidence

ORD record
ord-1decf52b79614667ab19326458dc1d51
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Reaction notes

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