Triethylamine → (R)-5-(4-Cyano-benzyl)-7-(3,5-dichloro-4-fluoro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carboxylic acid{1-[1-(5-iodo-pyrimidin-2-yl)-cyclopropylcarbamoyl]-cyclopropyl}-amide

HRID 2038769Notes

Reaction equation

HRID 2038769 reaction equation
Cl.Cl.[I:3][C:4]1[CH:5]=[N:6][C:7]([C:10]2([NH:13][C:14]([C:16]3([NH2:19])[CH2:18][CH2:17]3)=[O:15])[CH2:12][CH2:11]2)=[N:8][CH:9]=1.C(N(CC)CC)C.[C:27]([C:29]1[CH:57]=[CH:56][C:32]([CH2:33][C@@:34]2([CH3:55])[N:38]3[C:39]([C:42](Cl)=[O:43])=[CH:40][N:41]=[C:37]3[N:36]([C:45]3[CH:50]=[C:49]([Cl:51])[C:48]([F:52])=[C:47]([Cl:53])[CH:46]=3)[C:35]2=[O:54])=[CH:31][CH:30]=1)#[N:28]>C1COCC1>[I:3][C:4]1[CH:9]=[N:8][C:7]([C:10]2([NH:13][C:14]([C:16]3([NH:19][C:42]([C:39]4[N:38]5[C@@:34]([CH2:33][C:32]6[CH:31]=[CH:30][C:29]([C:27]#[N:28])=[CH:57][CH:56]=6)([CH3:55])[C:35](=[O:54])[N:36]([C:45]6[CH:46]=[C:47]([Cl:53])[C:48]([F:52])=[C:49]([Cl:51])[CH:50]=6)[C:37]5=[N:41][CH:40]=4)=[O:43])[CH2:18][CH2:17]3)=[O:15])[CH2:12][CH2:11]2)=[N:6][CH:5]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 683791511-Amino-cyclopropanecarboxylic acid[1-(5-iodo-pyrimidin-2-yl)-cyclopropyl]-amide dihydrochlorideHCID 86671823(R)-5-(4-Cyano-benzyl)-7-(3,5-dichloro-4-fluoro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl chloride

Product 1

HCID 68379434(R)-5-(4-Cyano-benzyl)-7-(3,5-dichloro-4-fluoro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carboxylic acid{1-[1-(5-iodo-pyrimidin-2-yl)-cyclopropylcarbamoyl]-cyclopropyl}-amideYield 101.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To 1-amino-cyclopropanecarboxylic acid[1-(5-iodo-pyrimidin-2-yl)-cyclopropyl]-amide dihydrochloride (400 mg, 0.96 mmol) was added 1 mL of dry THF and triethylamine (0.71 ml, 3.98 mmol). Crude (R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-4-fluoro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl chloride (476 mg, 1.0 mmol) was dissolved in 2 mL of dry THF and transferred to the reaction flask. After 2 h, the solvent was removed at 55° C. under a stream of N2. The resulting slurry was diluted with EtOAc (75 mL) and washed with 10% aq citric acid (75 mL) and saturated aq NaHCO3 (75 mL). The organic layer was dried over Na2SO4 and concentrated to give a light orange foam. This solid was purified by normal phase flash chromatography on silica gel (1→3% MeOH/CH2Cl2) to give 767 mg of the title compound as a tan powder, m/z 785.5.

Workup

  1. customthe solvent was removed at 55° C. under a stream of N2
  2. additionThe resulting slurry was diluted with EtOAc (75 mL)
  3. washwashed with 10% aq citric acid (75 mL) and saturated aq NaHCO3 (75 mL)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. concentrationconcentrated
  6. customto give a light orange foam
  7. customThis solid was purified by normal phase flash chromatography on silica gel (1→3% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-68e65e0ed9ae44e7af22065b46461e27
Source dataset
uspto-grants-2013_11
Patent number
US08575360B2

Reaction notes

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