2-Thiophenecarbonyl chloride → 6-{[(3-Fluoro-4-morpholin-4-yl-phenyl)-(thiophene-2-carbonyl)-amino]methyl}-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester

HRID 1452938Notes

Reaction equation

HRID 1452938 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]2[CH:10]([CH:11]2[CH2:14][NH:15][C:16]2[CH:21]=[CH:20][C:19]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)=[C:18]([F:28])[CH:17]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.[S:38]1[CH:42]=[CH:41][CH:40]=[C:39]1[C:43](Cl)=[O:44].C([O-])(O)=O.[Na+]>ClCCCl>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH:10]2[CH:12]([CH:11]2[CH2:14][N:15]([C:16]2[CH:21]=[CH:20][C:19]([N:22]3[CH2:23][CH2:24][O:25][CH2:26][CH2:27]3)=[C:18]([F:28])[CH:17]=2)[C:43]([C:39]2[S:38][CH:42]=[CH:41][CH:40]=2)=[O:44])[CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 789282-Thiophenecarbonyl chlorideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 690387116-[(3-Fluoro-4-morpholin-4-yl-phenylamino)-methyl]-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester

Product 1

HCID 690366556-{[(3-Fluoro-4-morpholin-4-yl-phenyl)-(thiophene-2-carbonyl)-amino]methyl}-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a stirring solution of 6-[(3-Fluoro-4-morpholin-4-yl-phenylamino)-methyl]-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester prepared above (500 mg, 1.28 mmol) in 10 mL of DCE at room temperature was added DIEA (0.33 mL, 1.92 mmol) and 2-thiophenecarbonylchloride (0.21 mL, 1.92 mmol). After 2 hours, saturated NaHCO3 was added, and the mixture was extracted with CH2Cl2. The combined extracts were dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The resulting crude material was taken up in 50% EtOAc/hexanes and the white solids were filtered off. The remaining filtrate was concentrated under reduce pressure to yield 640 mg of the desired product. 400 MHz 1H NMR (CDCl3) δ 7.26-7.28 (m, 1H), 6.83-7.15 (m, 4H), 6.76-6.78 (m, 1H), 3.79-3.85 (m, 5H), 3.54-3.59 (m, 1H), 3.44 (d, J=11.0 Hz, 1H), 3.39 (d, J=11.0 Hz, 1H), 3.21-3.26 (m, 2H), 3.08-3.10 (m, 4H), 1.36-1.38 (m, 11H), 0.81-0.86 (m, 1H); MS M+1)

Workup

  1. extractionthe mixture was extracted with CH2Cl2
  2. dry with materialThe combined extracts were dried over anhydrous MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. filtrationthe white solids were filtered off
  6. concentrationThe remaining filtrate was concentrated

Sources & evidence

ORD record
ord-8bbb2eaf596f4e019e78d4c9c2a25a91
Source dataset
uspto-grants-2009_01
Patent number
US07473787B2

Reaction notes

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