4,6-Dichloro-2-methylpyrimidine → 2-{6-[(6-Chloro-2-methylpyrimidin-4-yl)oxy]-2,3-dihydro-4h-1,4-benzoxazin-4-yl}-6,6-dimethyl-6,7-dihydro[1,3]thiazolo[5,4-c]pyridin-4(5h)-one

HRID 885990Notes

Reaction equation

HRID 885990 reaction equation
[CH3:1][C:2]1([CH3:23])[NH:7][C:6](=[O:8])[C:5]2[S:9][C:10]([N:12]3[C:17]4[CH:18]=[C:19]([OH:22])[CH:20]=[CH:21][C:16]=4[O:15][CH2:14][CH2:13]3)=[N:11][C:4]=2[CH2:3]1.[Cl:24][C:25]1[CH:30]=[C:29](Cl)[N:28]=[C:27]([CH3:32])[N:26]=1.CC(C)([O-])C.[Na+]>C1COCC1>[Cl:24][C:25]1[N:26]=[C:27]([CH3:32])[N:28]=[C:29]([O:22][C:19]2[CH:20]=[CH:21][C:16]3[O:15][CH2:14][CH2:13][N:12]([C:10]4[S:9][C:5]5[C:6](=[O:8])[NH:7][C:2]([CH3:23])([CH3:1])[CH2:3][C:4]=5[N:11]=4)[C:17]=3[CH:18]=2)[CH:30]=1

Participants

5

Reactant 3

HCID 2349974,6-Dichloro-2-methylpyrimidineHCID 23676156Sodium t-butoxideHCID 671855836,6-Dimethyl-2-(6-hydroxy-2,3-dihydrobenzo[1,4]oxazin-4-yl)-6,7-dihydro-[1,3]thiazolo[5,4-c]pyridin-4(5h)-one

Product 1

HCID 248558182-{6-[(6-Chloro-2-methylpyrimidin-4-yl)oxy]-2,3-dihydro-4h-1,4-benzoxazin-4-yl}-6,6-dimethyl-6,7-dihydro[1,3]thiazolo[5,4-c]pyridin-4(5h)-oneYield 35%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
155 °C

Procedure

To a suspension of Example 57 (70 mg, 0.211 mmol) in THF (4 mL) was added 4,6-dichloro-2-methylpyrimidine (86 mg, 0.529 mmol) and sodium tert-butoxide (81 mg, 0.846 mmol). The reaction was heated to 155° C. under microwave irradiation for 30 minutes then cooled to room temperature. The mixture was partitioned between DCM (50 mL) and water (50 mL); the organic phase was washed with brine (50 mL), dried (MgSO4), and concentrated in vacuo. The residue was purified by preparative HPLC (Method 6) to give the title compound (32 mg, 35%) as an off-white solid. δH (CDCl3) 8.02 (1H, d, J 2.8 Hz), 6.99 (1H, d, J 8.9 Hz), 6.82 (1H, dd, J 8.9 and 2.6 Hz), 6.66 (1H, s), 5.50 (1H, s), 4.47-4.26 (2H, m), 4.19-4.04 (2H, m), 2.86 (2H, s), 2.61 (3H, s), 1.38 (6H, s). LCMS (ES+) 458.0 (M+H)+, RT 3.50 minutes (Method 1).

Workup

  1. temperaturethen cooled to room temperature
  2. customThe mixture was partitioned between DCM (50 mL) and water (50 mL)
  3. washthe organic phase was washed with brine (50 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by preparative HPLC (Method 6)

Sources & evidence

ORD record
ord-66f80fb4eb0e459287bdd6688f5853b9
Source dataset
uspto-grants-2012_08
Patent number
US08242116B2

Reaction notes

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