Dimethylformamide → HCID 89832333, compound

HRID 338149Notes

Reaction equation

HRID 338149 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]23[CH2:16][N:15]([C:17]4[N:22]=[CH:21][C:20]([F:23])=[CH:19][N:18]=4)[CH2:14][CH:13]2[CH2:12][S:11][C:10]([NH:24][C:25](=[O:32])[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[N:9]3)[CH:5]=[CH:6][CH:7]=1.[CH3:33][N:34](C)C=O>[C-]#N.[Zn+2].[C-]#N.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:33]([C:2]1[CH:3]=[C:4]([C:8]23[CH2:16][N:15]([C:17]4[N:22]=[CH:21][C:20]([F:23])=[CH:19][N:18]=4)[CH2:14][CH:13]2[CH2:12][S:11][C:10]([NH:24][C:25](=[O:32])[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[N:9]3)[CH:5]=[CH:6][CH:7]=1)#[N:34]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 89832315HCID 89832315, compound

Product 1

HCID 89832333HCID 89832333, compoundYield 67%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

To a solution of racemic N-[7a-(3-bromophenyl)-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide (310 mg, 605 μmol) and zinc cyanide (170 mg, 1.42 mmol) in dimethylformamide (6.0 mL) is added tetrakis(triphenylphosphine) palladium (200 mg, 171 μmol). The resulting mixture is heated at 100° C. under N2 for 16.5 hours before being cooled to room temperature, filtered through diatomaceous earth, and washed with ethyl acetate (30 mL). The combined filtrate is washed with semi-saturated sodium bicarbonate solution (50 mL), extracted with ethyl acetate (30 mL), and chloroform (30 mL). The combined organic layers are dried over magnesium sulfate, filtered, and concentrated to dryness. The residue is purified by silica gel flash chromatography, eluting with a gradient of ethyl acetate/dichloromethane (0 to 30%) to give the title compound (187 mg, 67%). EI/MS (m/e): 459.0 (M+H).

Workup

  1. temperaturebefore being cooled to room temperature
  2. filtrationfiltered through diatomaceous earth
  3. washwashed with ethyl acetate (30 mL)
  4. washThe combined filtrate is washed with semi-saturated sodium bicarbonate solution (50 mL)
  5. extractionextracted with ethyl acetate (30 mL), and chloroform (30 mL)
  6. dry with materialThe combined organic layers are dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customThe residue is purified by silica gel flash chromatography
  10. washeluting with a gradient of ethyl acetate/dichloromethane (0 to 30%)

Sources & evidence

ORD record
ord-574d5af041d540e9878262f09f18fe71
Source dataset
uspto-grants-2014_11
Patent number
US08889856B2

Reaction notes

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