4-Hydroxypyrimidine → 3-[2-((R)-3-piperidin-1-yl-pyrrolidin-1-yl)-benzothiazol-6-yl]-3H-pyrimidin-4-one

HRID 2041000Notes

Reaction equation

HRID 2041000 reaction equation
Br[C:2]1[CH:21]=[CH:20][C:5]2[N:6]=[C:7]([N:9]3[CH2:13][CH2:12][C@@H:11]([N:14]4[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]4)[CH2:10]3)[S:8][C:4]=2[CH:3]=1.[N:22]1[CH:27]=[CH:26][C:25](=[O:28])[NH:24][CH:23]=1.CN[C@@H]1CCCC[C@H]1NC>N1C=CC=CC=1.CCOCC.[Cu].[Cu]I>[N:14]1([C@@H:11]2[CH2:12][CH2:13][N:9]([C:7]3[S:8][C:4]4[CH:3]=[C:2]([N:24]5[C:25](=[O:28])[CH:26]=[CH:27][N:22]=[CH:23]5)[CH:21]=[CH:20][C:5]=4[N:6]=3)[CH2:10]2)[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1

Participants

8

Reactant 3

HCID 206954-HydroxypyrimidineHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 44124247(R)-6-bromo-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazole

Product 1

HCID 441253323-[2-((R)-3-piperidin-1-yl-pyrrolidin-1-yl)-benzothiazol-6-yl]-3H-pyrimidin-4-one

Reagents, catalysts & solvents 4

HCID 23978CopperCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1049PyridineSolventHCID 3283Diethyl EtherSolvent

Procedure

A solution of (R)-6-bromo-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazole (Example 14, 80 mg, 0.218 mmol), pyrimidin-4(3H)-one (31.5 mg, 0.328 mmol), (1R,2R)—N1,N2-dimethylcyclohexane-1,2-diamine (31.1 mg, 0.218 mmol), copper (27.8 mg, 0.437 mmol) and copper(I) iodide (8.32 mg, 0.044 mmol) in pyridine (3 ml) was heated in a microwave reactor to 200° C. for 30 minutes. The mixture was diluted with ether (20 mL) and washed with water, a small amount of aqueous NH4OH and brine. The organic layer was separated and dried with MgSO4 and concentrated under reduced pressure. The residue obtained was chromatographed on silica gel column eluting with 3% (9:1 methanol:concentrated NH4OH) in dichloromethane to provide the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 1.43-1.52 (m, 2H), 1.58-1.69 (m, 4H), 1.94-2.11 (m, 1H), 2.25-2.37 (m, 1H), 2.39-2.58 (m, 4H), 2.96-3.09 (m, 1H), 3.40-3.63 (m, 2H), 3.72-3.92 (m, 2H), 6.56 (d, J=6.74 Hz, 1H), 7.22 (dd, J=8.72, 2.38 Hz, 1H), 7.62 (d, J=2.38 Hz, 1H), 7.65 (d, J=8.33 Hz, 1H), 7.94 (d, J=6.74 Hz, 1H), 8.20 (s, 1H); MS (DCI/NH3) m/z 382 (M+H)+.

Workup

  1. washwashed with water
  2. customThe organic layer was separated
  3. dry with materialdried with MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue obtained
  6. customwas chromatographed on silica gel column
  7. washeluting with 3% (9:1 methanol:concentrated NH4OH) in dichloromethane

Sources & evidence

ORD record
ord-b77a64eaa7904d0da26025eaeabd0cd0
Source dataset
uspto-grants-2013_11
Patent number
US08580968B2

Reaction notes

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