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

HRID 1452940Notes

Reaction equation

HRID 1452940 reaction equation
FC(F)(F)C(O)=O.[CH:8]12[CH:13]([CH2:14][N:15]([C:23]3[CH:28]=[CH:27][C:26]([N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)=[C:25]([F:35])[CH:24]=3)[C:16]([C:18]3[S:19][CH:20]=[CH:21][CH:22]=3)=[O:17])[CH:12]1[CH2:11][NH:10][CH2:9]2.[CH:36](=O)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>C(Cl)Cl>[CH2:36]([N:10]1[CH2:11][CH:12]2[CH:8]([CH:13]2[CH2:14][N:15]([C:23]2[CH:28]=[CH:27][C:26]([N:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)=[C:25]([F:35])[CH:24]=2)[C:16]([C:18]2[S:19][CH:20]=[CH:21][CH:22]=2)=[O:17])[CH2:9]1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

Participants

4

Reactant 2

HCID 240BenzaldehydeHCID 86597825Thiophene-2-carboxylic acid (3-aza-bicyclo[3.1.0]hex-6-ylmethyl)-(3-fluoro-4-morpholin-4-yl-phenyl)-amide trifluoroacetic acid salt

Product 1

HCID 86597826Thiophene-2-carboxylic acid (3-benzyl-3-aza-bicyclo[3.1.0]hex-6-ylmethyl)-(3-fluoro-4-morpholin-4-yl-phenyl)-amide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirring solution of the Thiophene-2-carboxylic acid (3-aza-bicyclo[3.1.0]hex-6-ylmethyl)-(3-fluoro-4-morpholin-4-yl-phenyl)-amide trifluoroacetic acid salt prepared above (100 mg, 0.16 mmol) in 4 mL of CH2Cl2 at room temperature was added benzaldehyde (0.02 mL, 0.24 mmol) and NaHB(OAc)3 (50 mg, 0.24 mmol). The reaction stirred at room temperature for 2 hours. The reaction was quenched by the addition of saturated NaHCO3, the layers were separated, and the aqueous layer was extracted with CH2Cl2. The combined organic layers were dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The resulting crude material was purified via flash chromatography with 75% EtOAc/hexanes. The product containing fractions were collected and concentrated to yield 32 mg of the desired product. 400 MHz 1H NMR (CDCl3) δ 7.17-7.29 (m, 6H), 6.94-6.98 (m, 4H), 6.78-6.80 (m, 1H), 3.86-3.88 (m, 4H), 3.65 (d, J=7.47 Hz, 2H), 3.52 (brs, 2H), 3.09-3.12 (m, 4H), 2.86-2.88 (m, 2H), 2.26-2.28 (m, 2H), 1.63 (brs, 1H), 1.47 (brs, 1H), 1.21-1.25 (m, 1H); MS (M+1) 492.2.

Workup

  1. customThe reaction was quenched by the addition of saturated NaHCO3
  2. customthe layers were separated
  3. extractionthe aqueous layer was extracted with CH2Cl2
  4. dry with materialThe combined organic layers were dried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting crude material was purified via flash chromatography with 75% EtOAc/hexanes
  8. additionThe product containing fractions
  9. customwere collected
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-22c2caa88f434dd894d4323835cb09ca
Source dataset
uspto-grants-2009_01
Patent number
US07473787B2

Reaction notes

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