Sulfuric Acid → 3(S)-(6-Methoxy-pyridin-3-yl)-3-{2-oxo-3-[3-(6,7,8,9-tetrahydro-5H-pyrido[2,3-b]azepin-2-yl)-propyl]-2,3-dihydro-imidazol-1-yl}-propionic acid tert-butyl ester

HRID 993246Notes

Reaction equation

HRID 993246 reaction equation
ClC(Cl)(O[C:5](=[O:11])OC(Cl)(Cl)Cl)Cl.[C:13]([O:17][C:18](=[O:36])[CH2:19][C@H:20]([NH:29][CH2:30][CH:31](OC)OC)[C:21]1[CH:22]=[N:23][C:24]([O:27][CH3:28])=[CH:25][CH:26]=1)([CH3:16])([CH3:15])[CH3:14].C(N(CC)CC)C.[N:44]1[C:49]2[NH:50][CH2:51][CH2:52][CH2:53][CH2:54][C:48]=2[CH:47]=[CH:46][C:45]=1[CH2:55][CH2:56][CH2:57][NH2:58].OS(O)(=O)=O>C1COCC1>[C:13]([O:17][C:18](=[O:36])[CH2:19][C@@H:20]([C:21]1[CH:22]=[N:23][C:24]([O:27][CH3:28])=[CH:25][CH:26]=1)[N:29]1[CH:30]=[CH:31][N:58]([CH2:57][CH2:56][CH2:55][C:45]2[CH:46]=[CH:47][C:48]3[CH2:54][CH2:53][CH2:52][CH2:51][NH:50][C:49]=3[N:44]=2)[C:5]1=[O:11])([CH3:14])([CH3:15])[CH3:16]

Participants

7

Reactant 5

HCID 1118Sulfuric AcidHCID 8471Triethylamine2×HCID 94429TriphosgeneHCID 111751973(S)-(2,2-dimethoxyethylamino)-3-(6-methoxypyridin-3-yl)propionate tert butyl esterHCID 184089753-(6,7,8,9-Tetrahydro-5H-pyrido[2,3-b]azepin-2-yl)-propylamine

Product 1

HCID 701276213(S)-(6-Methoxy-pyridin-3-yl)-3-{2-oxo-3-[3-(6,7,8,9-tetrahydro-5H-pyrido[2,3-b]azepin-2-yl)-propyl]-2,3-dihydro-imidazol-1-yl}-propionic acid tert-butyl esterYield 208.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of triphosgene (0.246 g, 0.804 mmol) in THF (5 mL) at 0° C. was added a mixture of 1-6 (0.78 g, 2.29 mmol), triethylamine (0.36 mL, 3.09 mmol) and THF (1 mL) over 10 minutes. After 30 minutes, the reaction was allowed to warm to ambient temperature and stir for 1 hour. The mixture was then purged with argon for 30 minutes, and to it was added a mixture of 3-6 (0.435 g, 2.52 mmol), triethylamine (0.36 mL, 3.09 mmol) and THF (5 mL). The mixture was then heated at 0° C. for 2 hours, allowed to cool to ambient temperature. 2M H2SO4 (2.5 mL) was then added, and the mixture stirred for 15 hours. The reaction was then quenched with a 10% w/v solution of K2CO3 (10 mL), diluted with ethyl acetate, washed with water and brine, dried over MgSO4, and concentrated to give 850 mg of 3-7 as a yellow oil, used crude in the next step.

Workup

  1. customThe mixture was then purged with argon for 30 minutes
  2. additionto it was added
  3. temperatureThe mixture was then heated at 0° C. for 2 hours
  4. temperatureto cool to ambient temperature
  5. stirringthe mixture stirred for 15 hours
  6. customThe reaction was then quenched with a 10% w/v solution of K2CO3 (10 mL)
  7. additiondiluted with ethyl acetate
  8. washwashed with water and brine
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-c565db741aff48ca86873d906c943edd
Source dataset
uspto-grants-2002_10
Patent number
US06472403B2

Reaction notes

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