Acetic Acid → HCID 178441315, compound

HRID 78549Notes

Reaction equation

HRID 78549 reaction equation
[C:1]([C:5]1[S:9]/[C:8](=[N:10]\[C:11](=[O:24])[C:12]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][C:13]=2[CH:22]=O)/[N:7]([CH2:25][C@H:26]2[CH2:30][CH2:29][CH2:28][O:27]2)[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH:31]1[CH2:34][CH2:33][CH2:32]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[N:31]1([CH2:22][C:13]2[CH:14]=[CH:15][C:16]([C:18]([F:19])([F:20])[F:21])=[CH:17][C:12]=2[C:11](/[N:10]=[C:8]2\[S:9][C:5]([C:1]([CH3:3])([CH3:2])[CH3:4])=[CH:6][N:7]\2[CH2:25][C@H:26]2[CH2:30][CH2:29][CH2:28][O:27]2)=[O:24])[CH2:34][CH2:33][CH2:32]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 10422AzetidineHCID 5049666Sodium triacetoxyborohydrideHCID 178441317HCID 178441317, compound

Product 1

HCID 178441315HCID 178441315, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a 20 mL vial, to a solution of Example 375C (52 mg, 0.118 mmol) in dichloromethane (2 mL) was added azetidine (20.22 mg, 0.354 mmol), followed by addition of acetic acid (7.09 mg, 0.118 mmol) and sodium triacetoxyborohydride (37.5 mg, 0.177 mmol) and the mixture was stirred for 2 hr. The reaction was quenched with saturated NaHCO3 and extracted with dichloromethane (3×5 mL). The organics were combined, dried, filtered, concentrated and the residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, gradient elution over 25 min with solvents A:B (100:0 to 10:90); solvent A=CH2Cl2; solvent B=7M NH3/MeOH (1):CH2Cl2 (9)) to afford the title compound in 79% yield. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.34 (s, 9H) 1.61-1.76 (m, 1H) 1.79-1.91 (m, 2H) 1.91-2.06 (m, 3H) 3.18 (t, J=6.94 Hz, 4H) 3.60-3.71 (m, 1H) 3.74-3.85 (m, 1H) 4.06 (s, 2H) 4.23-4.36 (m, 3H) 7.32 (s, 1H) 7.74-7.78 (m, 2H) 8.21-8.25 (m, 1H); MS (DCI/NH3) m/z 482 (M+H)+. Anal. calcd C25H32F3N3O2S.0.3 C6H6: C, 62.02; H, 6.56; N, 8.10. Found: C, 61.94; H, 6.43; N, 8.38.

Workup

  1. customThe reaction was quenched with saturated NaHCO3
  2. extractionextracted with dichloromethane (3×5 mL)
  3. customdried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customthe residue was purified by column chromatography
  7. washan Analogix® Intelliflash280™ (SiO2, gradient elution over 25 min with solvents A:B (100:0 to 10:90); solvent A=CH2Cl2; solvent B=7M NH3/MeOH (1):CH2Cl2 (9))

Sources & evidence

ORD record
ord-79c38e6b88e14695b1379058c0df1dfc
Source dataset
uspto-grants-2014_09
Patent number
US08841334B2

Reaction notes

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