Diisopropylethylamine → Thiophene-2-carboxylic acid [3-(4-ethyl-benzoyl)-3-aza-bicyclo[3.1.0]hex-6-ylmethyl]-(3-fluoro-4-morpholin-4-yl-phenyl)-amide

HRID 1452941Notes

Reaction equation

HRID 1452941 reaction equation
[CH:1]12[CH:6]([CH2:7][N:8]([C:16]3[CH:21]=[CH:20][C:19]([N:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)=[C:18]([F:28])[CH:17]=3)[C:9]([C:11]3[S:12][CH:13]=[CH:14][CH:15]=3)=[O:10])[CH:5]1[CH2:4][NH:3][CH2:2]2.CCN(C(C)C)C(C)C.[CH2:38]([C:40]1[CH:48]=[CH:47][C:43]([C:44](Cl)=[O:45])=[CH:42][CH:41]=1)[CH3:39]>C(Cl)Cl>[CH2:38]([C:40]1[CH:48]=[CH:47][C:43]([C:44]([N:3]2[CH2:4][CH:5]3[CH:1]([CH:6]3[CH2:7][N:8]([C:16]3[CH:21]=[CH:20][C:19]([N:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)=[C:18]([F:28])[CH:17]=3)[C:9]([C:11]3[S:12][CH:13]=[CH:14][CH:15]=3)=[O:10])[CH2:2]2)=[O:45])=[CH:42][CH:41]=1)[CH3:39]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 853684-Ethylbenzoyl chlorideHCID 72401275Thiophene-2-carboxylic acid (3-aza-bicyclo[3.1.0]hex-6-ylmethyl)-(3-fluoro-4-morpholin-4-yl-phenyl)-amide

Product 1

HCID 11752961Thiophene-2-carboxylic acid [3-(4-ethyl-benzoyl)-3-aza-bicyclo[3.1.0]hex-6-ylmethyl]-(3-fluoro-4-morpholin-4-yl-phenyl)-amideYield 72.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirring solution of thiophene-2-carboxylic acid (3-aza-bicyclo[3.1.0]hex-6-ylmethyl)-(3-fluoro-4-morpholin-4-yl-phenyl)-amide (50 mg, 0.13 mmol) in 3 mL of anhydrous CH2Cl2, was added DIEA (0.065 mL, 0.37 mmol), followed by 4-ethylbenzoyl chloride (0.02 mL, 0.14 mmol). The reaction was stirred at room temperature for 1 hour, quenched with saturated NaHCO3, and extracted with CH2Cl2. The combined extracts were dried over anhydrous MgSO4, filtered and concentrated. The resulting crude material was purified via flash chromatography with 75% EtOAc/hexanes. The product containing fractions were collected and concentrated to yield 50 mg of a clear colorless oil. 400 MHz 1H NMR (CDCl3) δ 7.25-7.28 (m, 3H), 7.14-7.16 (m, 2H), 6.82-6.92 (m, 4H), 6.76-6.78 (m, 1H), 4.02-4.09 (m, 1H), 3.84-3.91 (m, 5H), 3.48-3.54 (m, 2H), 3.37-3.44 (m, 2H), 3.08-3.11 (m, 4H), 2.60 (q, 2H), 1.45 (s, 2H), 1.16-1.19 (m, 3H), 0.82-0.85 (m, 1H); MS (M+1) 534.2.

Workup

  1. customquenched with saturated NaHCO3
  2. extractionextracted with CH2Cl2
  3. dry with materialThe combined extracts were dried over anhydrous MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting crude material was purified via flash chromatography with 75% EtOAc/hexanes
  7. additionThe product containing fractions
  8. customwere collected
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-c61178f907074b8e8af10f5decbb3fc4
Source dataset
uspto-grants-2009_01
Patent number
US07473787B2

Reaction notes

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