Dimethylformamide → HCID 68891810, compound

HRID 857894Notes

Reaction equation

HRID 857894 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[C:14]([CH:19]3[CH2:21][CH2:20]3)=[CH:15][C:16]([C:17]#[N:18])=[C:10]2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(O[C:27]([N:29]1CCN2C(C3CC3)=C(C#N)C=C2C1)=O)(C)(C)C.ClS(N=C=O)(=O)=O.CN(C)C=O>C(#N)C.C(N(CC)CC)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[C:14]([CH:19]3[CH2:20][CH2:21]3)=[C:15]([C:27]#[N:29])[C:16]([C:17]#[N:18])=[C:10]2[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 70918Chlorosulfonyl isocyanateHCID 68887555HCID 68887555, compoundHCID 68889832HCID 68889832, compound

Product 1

HCID 68891810HCID 68891810, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent

Procedure

A stirred solution of a mixture of 8-cyano-6-cyclopropyl-3,4-dihydro-1H-pyrrolo[1,2-a]pyrazine-2-carboxylic acid tert-butyl ester and 7-cyano-6-cyclopropyl-3,4-dihydro-1H-pyrrolo[1,2-a]pyrazine-2-carboxylic acid tert-butyl ester (6.67 g, Reference Example 9) in dry acetonitrile (370 mL) under a blanket of nitrogen at 0° C. was treated with chlorosulfonyl isocyanate (2.75 mL) dropwise whilst maintaining the temperature below 5° C. After stirring below 5° C. for a further 2.5 hours the reaction mixture was treated with dimethylformamide (18.5 mL), allowed to warm to room temperature and then stirred for a further 1 hour. The reaction mixture was then treated with triethylamine (21.7 mL), stirred for a further 1 hour and then left to stand overnight. The reaction mixture was evaporated and the residue treated with dichloromethane (200 mL) and water (80 mL). The organic phase was separated, further washed with water (80 mL), then dried over magnesium sulfate and evaporated. The residue was subjected to column chromatography on silica eluting with a mixture of ethyl acetate and pentane (2:3, v/v) to give the title compound (4.97 g) as a yellow oil, Rf 0.29 (ethyl acetate:pentane, 2:3). 1H NMR [(CDCl3]: δ 4.70 (s, 2H), 4.03 (t, 2H), 3.87 (t, 2H) 1.73–1.65 (m, 1H), 1.51 (s, 9H), 1.14–1.07 (m, 2H) and 0.99–0.93 (m, 2H).

Workup

  1. temperaturewhilst maintaining the temperature below 5° C
  2. stirringstirred for a further 1 hour
  3. stirringstirred for a further 1 hour
  4. waitleft
  5. waitto stand overnight
  6. customThe reaction mixture was evaporated
  7. additionthe residue treated with dichloromethane (200 mL) and water (80 mL)
  8. customThe organic phase was separated
  9. washfurther washed with water (80 mL)
  10. dry with materialdried over magnesium sulfate
  11. customevaporated
  12. additionThe residue was subjected to column chromatography on silica eluting with a mixture of ethyl acetate and pentane (2:3

Sources & evidence

ORD record
ord-cf82a0acea284a7888c15db885a77d9d
Source dataset
uspto-grants-2006_12
Patent number
US07148215B2

Reaction notes

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