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N-methyl-2-pyrrolidone → (r)-4'-Methyl-5-thiazol-2-yl-biphenyl-3-carboxylic acid (1-methyl-2-morpholin-4-yl-ethyl)-amide

HRID 1888914
Notes
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Reaction equation

HRID 1888914 reaction equation
CCN=C=NCCCN(C)C.[CH3:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[C:23]([C:25]3[S:26][CH:27]=[CH:28][N:29]=3)[CH:22]=[C:21]([C:30]([OH:32])=O)[CH:20]=2)=[CH:15][CH:14]=1.C1C=CC2N(O)N=NC=2C=1.CN1C(=O)CCC1.[CH3:50][C@H:51]([NH2:59])[CH2:52][N:53]1[CH2:58][CH2:57][O:56][CH2:55][CH2:54]1>C(Cl)Cl>[CH3:50][C@@H:51]([NH:59][C:30]([C:21]1[CH:20]=[C:19]([C:16]2[CH:17]=[CH:18][C:13]([CH3:12])=[CH:14][CH:15]=2)[CH:24]=[C:23]([C:25]2[S:26][CH:27]=[CH:28][N:29]=2)[CH:22]=1)=[O:32])[CH2:52][N:53]1[CH2:58][CH2:57][O:56][CH2:55][CH2:54]1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 5

HCID 13387N-methyl-2-pyrrolidoneHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 7004115(S)-4-(2-Amino-propan-1-yl)-morpholineHCID 594325694'-Methyl-5-thiazol-2-yl-biphenyl-3-carboxylic acid

Product 1

HCID 59432539
(r)-4'-Methyl-5-thiazol-2-yl-biphenyl-3-carboxylic acid (1-methyl-2-morpholin-4-yl-ethyl)-amide
Yield 81%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

EDCI (54.0 mg, 0.282 mmol) was added in one portion at 0° C. to a solution of 4′-methyl-5-thiazol-2-yl-biphenyl-3-carboxylic acid (63 mg, 0.214 mmol), HOBt (40.0 mg, 0.296 mmol) and NMP (101.5 mg, 1.0 mmol) in CH2Cl2 (3 mL). After the reaction stirred at 0° C. for 1 hour, (S)-1-Methyl-2-morpholin-4-yl-ethylamine (50.0 mg, 0.230 mmol) was added. The reaction mixture was allowed to warm to room temperature and was stirred overnight. Solvent was removed under reduced pressure and the residue was purified by column chromatography (EtOAc) to afford (R)-4′-methyl-5-thiazol-2-yl-biphenyl-3-carboxylic acid (1-methyl-2-morpholin-4-yl-ethyl)-amide as a white solid (72 mg, 81%). MS (M+H)=422.

Workup

  1. temperatureto warm to room temperature
  2. stirringwas stirred overnight
  3. customSolvent was removed under reduced pressure
  4. customthe residue was purified by column chromatography (EtOAc)

Sources & evidence

ORD record
ord-cb546bf72b654488ab383efe62fab951
Source dataset
uspto-grants-2013_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08501933B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes