Dimethylformamide → HCID 86664055, compound

HRID 712347Notes

Reaction equation

HRID 712347 reaction equation
Br[C:2]1[C:10]2[S:9][C:8]([NH:11][C:12](=[O:16])[NH:13][CH2:14][CH3:15])=[N:7][C:6]=2[CH:5]=[C:4]([C:17]2[CH:18]=[N:19][C:20]([N:23]3[CH2:28][CH2:27][C:26]([CH3:34])([C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH2:25][CH2:24]3)=[N:21][CH:22]=2)[CH:3]=1.[CH3:35][N:36](C=O)C>[C-]#N.[Zn+2].[C-]#N.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>[C:35]([C:2]1[C:10]2[S:9][C:8]([NH:11][C:12](=[O:16])[NH:13][CH2:14][CH3:15])=[N:7][C:6]=2[CH:5]=[C:4]([C:17]2[CH:22]=[N:21][C:20]([N:23]3[CH2:24][CH2:25][C:26]([CH3:34])([C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH2:27][CH2:28]3)=[N:19][CH:18]=2)[CH:3]=1)#[N:36]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 86663956Ethyl 1-(5-(7-bromo-2-(3-ethylureido)benzo[d]thiazol-5-yl)pyrimidin-2-yl)-4-methylpiperidine-4-carboxylate

Product 1

HCID 86664055HCID 86664055, compoundYield 100%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
100 °C

Procedure

Ethyl 1-[5-[7-bromo-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate (600 mg, 0.658 mmol), zinc cyanide (96 mg, 0.822 mmol) and Pd(PPh3)4 (76 mg, 0.066 mmol) were suspended in DMF (10 mL) and degassed/purged (×3) with Ar. The reaction mixture was then heated at 100° C. under microwave irradiation for 40 mins, cooled to rt, diluted with EtOAc (50 mL), washed with water, brine and separated. The organic fraction was dried (Na2SO4) and concentrated under reduced pressure and the resulting solid purified by flash column chromatography (40 g GraceResolv silica cartridge—dry loaded), eluting with 0-10% MeOH/CH2Cl2. The resulting residue was washed with MeOH to afford desired compound (327 mg, ˜100%) as an off-white solid. MS: 494.14 [M+H]+.

Workup

  1. customdegassed/purged (×3) with Ar
  2. temperaturecooled to rt
  3. additiondiluted with EtOAc (50 mL)
  4. washwashed with water, brine
  5. customseparated
  6. dry with materialThe organic fraction was dried (Na2SO4)
  7. concentrationconcentrated under reduced pressure
  8. customthe resulting solid purified by flash column chromatography (40 g GraceResolv silica cartridge—dry loaded)
  9. washeluting with 0-10% MeOH/CH2Cl2
  10. washThe resulting residue was washed with MeOH

Sources & evidence

ORD record
ord-130554a0a426489fad77ce1136388632
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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