1,2-Dimethoxyethane → [2-(4-Methoxy-phenyl)-ethyl]-(2-methoxy-6-quinolin-6-yl-pyrimidin-4-yl)-amine

HRID 216109Notes

Reaction equation

HRID 216109 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]([O:19][CH3:20])=[CH:15][CH:14]=2)[CH:3]=1.[N:21]1[C:30]2[C:25](=[CH:26][C:27](B(O)O)=[CH:28][CH:29]=2)[CH:24]=[CH:23][CH:22]=1.COCCOC>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.O>[CH3:20][O:19][C:16]1[CH:17]=[CH:18][C:13]([CH2:12][CH2:11][NH:10][C:4]2[CH:3]=[C:2]([C:27]3[CH:26]=[C:25]4[C:30](=[CH:29][CH:28]=3)[N:21]=[CH:22][CH:23]=[CH:24]4)[N:7]=[C:6]([O:8][CH3:9])[N:5]=2)=[CH:14][CH:15]=1

Participants

6

Reactant 3

HCID 80711,2-DimethoxyethaneHCID 4192671Quinolin-6-ylboronic Acid (contains varying amounts of Anhydride)2×HCID 57636025(6-Chloro-2-methoxy-pyrimidin-4-yl)-[2-(4-methoxyphenyl)-ethyl]amine2×

Product 1

HCID 11523888[2-(4-Methoxy-phenyl)-ethyl]-(2-methoxy-6-quinolin-6-yl-pyrimidin-4-yl)-amineYield 71%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

A mixture of (6-chloro-2-methoxy-pyrimidin-4-yl)-[2-(4-methoxy-phenyl)-ethyl]-amine (150 mg, 0.51 mmol, Intermediate (8) prepared as described in Example 2 step 1), quinoline-6-boronic acid [176 mg, 1.02 mmol, Intermediate (22)], Cs2CO3 (590 mg, 1.81 mmol) tetrakis(triphenylphosphine)palladium (0) (59 mg, 0.051 mmol), ethylene glycol dimethyl ether (4 mL) and water (1 mL) is placed in a microwave tube, sealed and evacuated and flushed with argon three times and irradiated in a microwave oven at 140° C. for 10 minutes. The reaction mixture is partitioned between EtOAc and water. The organic phase is separated, washed with saturated sodium bicarbonate solution, dried over magnesium sulfate and evaporated. The residual solid is subjected to flash column chromatography on silica gel eluting with a mixture of EtOAc and heptane. The material is recrystallized from MeOH to afford [2-(4-methoxy-phenyl)-ethyl]-(2-methoxy-6-quinolin-6-yl-pyrimidin-4-yl)-amine [140 mg, 71%, Example 10(a)] LCMS: RT=5.97 minutes, MS: 387 (M+H). IC50=0.6 nM

Workup

  1. customis placed in a microwave tube
  2. customsealed
  3. customevacuated
  4. customflushed with argon three times
  5. customirradiated in a microwave oven at 140° C. for 10 minutes
  6. customThe reaction mixture is partitioned between EtOAc and water
  7. customThe organic phase is separated
  8. washwashed with saturated sodium bicarbonate solution
  9. dry with materialdried over magnesium sulfate
  10. customevaporated
  11. additionThe residual solid is subjected to flash column chromatography on silica gel eluting with a mixture of EtOAc and heptane
  12. customThe material is recrystallized from MeOH

Sources & evidence

ORD record
ord-ab74a1f5e3484e17b3321988b2fde434
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Reaction notes

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