Hydrochloric Acid → Cis(+/-)-5-(aminocarbonyl)-2-(4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)-1,3-thiazole-4-carboxylic acid

HRID 1948328Notes

Reaction equation

HRID 1948328 reaction equation
[Cl:1][C:2]1[C:6]([Cl:7])=[C:5]([CH3:8])[NH:4][C:3]=1[C:9]([NH:11][C@H:12]1[CH2:17][CH2:16][NH:15][CH2:14][C@H:13]1[O:18][CH3:19])=[O:10].[NH2:20][C:21]([C:23]1[S:27][C:26](Cl)=[N:25][C:24]=1[C:29]([O:31]CC)=[O:30])=[O:22].C([O-])([O-])=O.[K+].[K+].Cl>CN1C(=O)CCC1.O>[NH2:20][C:21]([C:23]1[S:27][C:26]([N:15]2[CH2:16][CH2:17][C@H:12]([NH:11][C:9]([C:3]3[NH:4][C:5]([CH3:8])=[C:6]([Cl:7])[C:2]=3[Cl:1])=[O:10])[C@H:13]([O:18][CH3:19])[CH2:14]2)=[N:25][C:24]=1[C:29]([OH:31])=[O:30])=[O:22]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 59406883Ethyl 5-(aminocarbonyl)-2-chloro-1,3-thiazole-4-carboxylate2×HCID 667076203,4-dichloro-N-[(3R,4S)-3-methoxypiperidin-4-yl]-5-methyl-1H-pyrrole-2-carboxamide2×

Product 1

HCID 86643341Cis(+/-)-5-(aminocarbonyl)-2-(4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)-1,3-thiazole-4-carboxylic acidYield 37.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
150 °C

Procedure

A solution of 55 mg (23 mmol) of Cis(±)-3,4-dichloro-N-[3-methoxypiperidin-4-yl]-5-methyl-1H-pyrrole-2-carboxamide (Intermediate 50), 55 mg (0.23 mmol) of ethyl 5-(aminocarbonyl)-2-chloro-1,3-thiazole-4-carboxylate (Intermediate 220) and 33 mg (0.23 mmol) K2CO3 in 3 ml NMP was heated at 150° C. for 1 h in a microwave reactor. Water (0.1 ml) was added and the mixture was heated at 150° C. for another hour. The solution was diluted with water and acidified with 1N HCl before being extracted 2 times with EtOAc. The EtOAc extracts were washed with brine, dried (MgSO4) and concentrated to give a solid that was triturated with MeOH to give 41 mg of a white solid. MS (ES) MH+: 479 for C17H19Cl2N5O5S; NMR: 1.75 (m, 2H), 2.2 (s, 3H), 3.3 (s), 3.5 (s, 1H), 3.9 (m, 1H), 4.2 (m, 2H), 7.15 (d, 1H), 7.8 (s, 1H), 8.9 (s, 1H), 12.2 (s, 1H).

Workup

  1. extractionbefore being extracted 2 times with EtOAc
  2. washThe EtOAc extracts were washed with brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customto give a solid
  6. customthat was triturated with MeOH

Sources & evidence

ORD record
ord-ae297838588e439680daa298a72f7cd0
Source dataset
uspto-grants-2013_03
Patent number
US08399489B2

Reaction notes

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