Diisopropylethylamine → HCID 90386202, compound

HRID 2170148Notes

Reaction equation

HRID 2170148 reaction equation
[NH2:1][N:2]1[CH:6]=[CH:5][C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[C:3]1[C:13]([O:15][CH3:16])=[O:14].[C:17]([NH:21][S:22]([C:25]1[S:26][CH:27]=[C:28](C(O)=O)[N:29]=1)(=[O:24])=[O:23])([CH3:20])([CH3:19])[CH3:18].CN([C:36]([O:40]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.O>[C:17]([NH:21][S:22]([C:25]1[S:26][C:27]([C:36]([NH:1][N:2]2[CH:6]=[CH:5][C:4]([C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)=[C:3]2[C:13]([O:15][CH3:16])=[O:14])=[O:40])=[CH:28][N:29]=1)(=[O:23])=[O:24])([CH3:18])([CH3:19])[CH3:20]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 670559302-(N-tert-butylsulfamoyl)thiazole-4-carboxylic acidHCID 90386150HCID 90386150, compound

Product 1

HCID 90386202HCID 90386202, compoundYield 29.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Methyl 1-amino-3-phenyl-1H-pyrrole-2-carboxylate (0.400 g, 1.85 mmol) and 2-(N-(tert-butyl)sulfamoyl)thiazole-4-carboxylic acid (0.733 g, 2.77 mmol) (Johnson et al., WO 2011/28741) were dissolved in DMF (10 mL) and cooled to 0° C. HATU (1.41 g, 3.70 mmol) was added slowly, followed by DIPEA (1.29 mL, 7.40 mmol). The reaction mixture was allowed to reach ambient temperature over 14 h and was diluted with water (25 mL) and extracted with ethylacetate (3×20 mL). The organic layer was separated and the combined organic portions dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography using CombiFlash (REDISEP®, silica gel, 40 g, 38% EtOAc/hexanes) to afford methyl 1-(2-(N-(tert-butyl)sulfamoyl)thiazole-5-carboxamido)-3-phenyl-1H-pyrrole-2-carboxylate (0.250 g, 29.2%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.26 (s, 9H), 3.50 (s, 3H), 6.31 (d, J=3.2 Hz, 1H), 7.25-7.43 (m, 6H), 8.39 (s, 1H), 8.77 (s, 1H), 11.83 (s, 1H).

Workup

  1. extractionextracted with ethylacetate (3×20 mL)
  2. customThe organic layer was separated
  3. dry with materialthe combined organic portions dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-048cc8a5f17747899af1001d4152d1f1
Source dataset
uspto-grants-2015_06
Patent number
US09050345B2

Reaction notes

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