Ammonium Chloride → 8-Carbamoyl-7-cyano-6-phenyl-3,4-dihydro-1H-pyrrolo[1,2-a]pyrazine-2-carboxylic acid tert-butyl ester

HRID 857896Notes

Reaction equation

HRID 857896 reaction equation
Cl.C[N:3](C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.[C:24]([O:28][C:29]([N:31]1[CH2:36][CH2:35][N:34]2[C:37]([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)=[C:38]([C:43]#[N:44])[C:39]([C:40](O)=[O:41])=[C:33]2[CH2:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25].[Cl-].[NH4+]>CN(C)C=O.C(N(CC)CC)C>[C:24]([O:28][C:29]([N:31]1[CH2:36][CH2:35][N:34]2[C:37]([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)=[C:38]([C:43]#[N:44])[C:39]([C:40](=[O:41])[NH2:3])=[C:33]2[CH2:32]1)=[O:30])([CH3:26])([CH3:25])[CH3:27]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 688892417-Cyano-6-phenyl-3,4-dihydro-1H-pyrrolo[1,2-a]pyrazine-2,8-dicarboxylic acid 2-tert-butyl ester

Product 1

HCID 688876928-Carbamoyl-7-cyano-6-phenyl-3,4-dihydro-1H-pyrrolo[1,2-a]pyrazine-2-carboxylic acid tert-butyl esterYield 86.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

A stirred solution of triethylamine (3.34 mL), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (2.30 g) and 1-hydroxybenzotriazole hydrate (1.62 g) in dry dimethylformamide (120 mL) was treated with 7-cyano-6-phenyl-3,4-dihydro-1H-pyrrolo[1,2-a]pyrazine-2,8-dicarboxylic acid 2-tert-butyl ester (4.40 g, Reference Example 19). After stirring at room temperature for a further 15 minutes the reaction mixture was treated with ammonium chloride (1.28 g) and then heated at 80° C. for 5 hours. The reaction mixture was allowed to cool to room temperature and then evaporated. The residue was treated with water and ethyl acetate. The organic phase was separated, washed with a 1M aqueous solution of sodium hydroxide (20 mL) and then water (20 mL). The organic phase was then dried over magnesium sulfate and evaporated to give a brown gum. The gum was triturated with diethyl ether to give the title compound (3.80 g) as a white solid, m.p. 214–215° C. 1H NMR [(CD3)2SO]: δ 7.59–7.50 (m, 5H), 7.41–7.27 (bs, 1H), 7.08–6.93 (bs, 1H), 4.75 (s, 2H), 3.92 (t, 2H), 3.62 (t, 2H) and 1.40 (s, 9H).

Workup

  1. temperatureheated at 80° C. for 5 hours
  2. temperatureto cool to room temperature
  3. customevaporated
  4. additionThe residue was treated with water and ethyl acetate
  5. customThe organic phase was separated
  6. washwashed with a 1M aqueous solution of sodium hydroxide (20 mL)
  7. dry with materialThe organic phase was then dried over magnesium sulfate
  8. customevaporated
  9. customto give a brown gum
  10. customThe gum was triturated with diethyl ether

Sources & evidence

ORD record
ord-1543c9e77cb94049a0d856fc8099f5d4
Source dataset
uspto-grants-2006_12
Patent number
US07148215B2

Reaction notes

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