Dimethylformamide → Ethyl 1-[5-[2-(3-ethyl-5-methyl-2-oxo-1,3,5-triazinan-1-yl)-7-formyl-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate

HRID 712321Notes

Reaction equation

HRID 712321 reaction equation
Br[C:2]1[C:10]2[S:9][C:8]([N:11]3[CH2:16][N:15]([CH3:17])[CH2:14][N:13]([CH2:18][CH3:19])[C:12]3=[O:20])=[N:7][C:6]=2[CH:5]=[C:4]([C:21]2[CH:22]=[N:23][C:24]([N:27]3[CH2:32][CH2:31][C:30]([CH3:38])([C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH2:29][CH2:28]3)=[N:25][CH:26]=2)[CH:3]=1.C(N(CC)CC)C.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([SiH](CC)CC)C.CN([CH:85]=[O:86])C>CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:18]([N:13]1[CH2:14][N:15]([CH3:17])[CH2:16][N:11]([C:8]2[S:9][C:10]3[C:2]([CH:85]=[O:86])=[CH:3][C:4]([C:21]4[CH:22]=[N:23][C:24]([N:27]5[CH2:32][CH2:31][C:30]([CH3:38])([C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH2:29][CH2:28]5)=[N:25][CH:26]=4)=[CH:5][C:6]=3[N:7]=2)[C:12]1=[O:20])[CH3:19]

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 12052TriethylsilaneHCID 812191,3-Bis(diphenylphosphino)propaneHCID 66977053Ethyl 1-[5-[7-bromo-2-(3-ethyl-5-methyl-2-oxo-1,3,5-triazinan-1-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate2×

Product 1

HCID 86664036Ethyl 1-[5-[2-(3-ethyl-5-methyl-2-oxo-1,3,5-triazinan-1-yl)-7-formyl-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylateYield 29%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
75 °C

Procedure

Ethyl 1-[5-[7-bromo-2-(3-ethyl-5-methyl-2-oxo-1,3,5-triazinan-1-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate (Intermediate 9) (2.58 g, 4.28 mmol) was dissolved in DMF (50 mL). Triethylamine (1.19 mL, 8.56 mmol), 1,3-bis(diphenylphosphino)propane (200 mg, 0.4 mmol), triethylsilane (2.05 mL, 12.8 mmol), Pd(OAc)2 (100 mg, 0.4 mmol) and Pd(dppf)Cl2DCM (200 mg, 0.2 mmol) were added and the mixture stirred at 75° C. for 32 h under an atmosphere of carbon monoxide (160 psi). The reaction mixture was cooled to rt, concentrated to dryness and the solid residue purified by flash column chromatography (80 g GraceResolv silica cartridge—dry loaded) eluting with 0-20% MeOH/CH2Cl2 to afford a brown solid. This solid was washed with EtOAc to afford the desired compound (690 mg, 29%) as an off-white solid. MS: 552.08 [M+H]+.

Workup

  1. temperatureThe reaction mixture was cooled to rt
  2. concentrationconcentrated to dryness
  3. customthe solid residue purified by flash column chromatography (80 g GraceResolv silica cartridge—dry loaded)
  4. washeluting with 0-20% MeOH/CH2Cl2
  5. customto afford a brown solid
  6. washThis solid was washed with EtOAc

Sources & evidence

ORD record
ord-1c12af3fdf2941ceb3f6c142367372f7
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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