Triethylamine → HCID 49805350, compound

HRID 2360559Notes

Reaction equation

HRID 2360559 reaction equation
[O:1]=[C:2]1[C:6]2([CH2:11][CH2:10][N:9]([C:12]3[S:13][C:14]([C:17]([OH:19])=O)=[CH:15][N:16]=3)[CH2:8][CH2:7]2)[N:5]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:4][NH:3]1.S(Cl)(Cl)=O.C(N(CC)CC)C.[NH2:37][C:38]1[CH:43]=[C:42]([C:44]2[S:45][CH:46]=[CH:47][CH:48]=2)[CH:41]=[CH:40][C:39]=1[NH:49]C(=O)OC(C)(C)C>C(Cl)Cl.C(O)(C(F)(F)F)=O.CN(C=O)C>[NH2:49][C:39]1[CH:40]=[CH:41][C:42]([C:44]2[S:45][CH:46]=[CH:47][CH:48]=2)=[CH:43][C:38]=1[NH:37][C:17]([C:14]1[S:13][C:12]([N:9]2[CH2:10][CH2:11][C:6]3([N:5]([C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=4)[CH2:4][NH:3][C:2]3=[O:1])[CH2:7][CH2:8]2)=[N:16][CH:15]=1)=[O:19]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 57717474tert-Butyl (2-amino-4-(thiophen-2-yl)phenyl)carbamateHCID 57717477HCID 57717477, compound

Product 1

HCID 49805350HCID 49805350, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 6422Trifluoroacetic acidSolvent

Procedure

2-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-8-yl)-1,3-thiazole-5-carboxylic acid (60 mg, 0.16 mmol) was made 0.25 M in anhydrous DCM and to this stirring solution was added catalytic DMF followed by 3 equivalents thionyl chloride (179 mg, 1.5 mmol). The resulting solution was stirred at ambient temperature under nitrogen for 1 hour. The reaction mixture was then concentrated in vacuo and azeotroped once with toluene to remove excess thionyl chloride. The residue was made 0.5M in anhydrous DCM and to this stirring solution was added 3 equivalents triethylamine (48 mg, 0.48 mmol) followed by 1 equivalent tert-butyl 2-amino-4-thien-2-ylphenylcarbamate (30 mg, 0.16 mmol). The resulting mixture was stirred at ambient temperature for 14 hours. The reaction mixture was then diluted with 4M TFA in DCM and allowed to stir at ambient temperature. After one hour the reaction mixture was concentrated in vacuo and purified by reverse phase chromatography: MS (ESI+): cal'd [M+H]+531.1, obs'd 531.1.

Workup

  1. concentrationThe reaction mixture was then concentrated in vacuo
  2. customazeotroped once with toluene
  3. customto remove excess thionyl chloride
  4. stirringThe resulting mixture was stirred at ambient temperature for 14 hours
  5. stirringto stir at ambient temperature
  6. concentrationAfter one hour the reaction mixture was concentrated in vacuo
  7. custompurified by reverse phase chromatography

Sources & evidence

ORD record
ord-b54be3f8745b49559cb691ca0943c0be
Source dataset
uspto-grants-2014_04
Patent number
US08686020B2

Reaction notes

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