Trifluoroacetic acid → HCID 131727015, compound

HRID 29171Notes

Reaction equation

HRID 29171 reaction equation
[C:1]1([CH3:10])[C:2]([C:7](Cl)=[O:8])=[CH:3][CH:4]=[CH:5][CH:6]=1.[NH2:11][C@@H:12]([CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C@H:13]([OH:33])[CH2:14][N:15](OC1CCCC1)[S:16]([C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=1)(=[O:18])=[O:17].F[C:42](F)(F)[C:43]([OH:45])=O.[CH:48](N(CC)C(C)C)([CH3:50])[CH3:49]>ClCCl>[CH2:34]([C@H:12]([NH:11][C:7](=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=1[CH3:10])[C@@H:13]([OH:33])[CH:14]([NH:15][S:16]([C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=1)(=[O:17])=[O:18])[O:45][CH:43]1[CH2:42][CH2:50][CH2:48][CH2:49]1)[C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 702762-Methylbenzoyl chlorideHCID 81531DiisopropylethylamineHCID 57010648N1-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl)-N1-(cyclopentyloxy)-4-methoxy-1-benzenesulfonamide

Product 1

HCID 131727015HCID 131727015, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

o-Toluoyl chloride (7.8 μL, 0.0602 mmol) was added to a solution of N1-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N1-(cyclopentyloxy)-4-methoxy-1-benzenesulfonamide×trifluoracetic acid (Step 1, Example 48), (30 mg, 0.055 mmol) and N,N-diisopropylethylamine (23.8 μL, 0.137 mmol) in approximately 1.5 mL of dichloromethane under Argon. After stirring for 18 hours at ambient temperature, the reaction solvent was removed in vacuo and the residue was purified on a preparative TLC plate (20×20 cm, 500 μM) eluting with 96:4 methylene chloride:methanol. The product band was removed, eluted with 4:1 methylene chloride:methanol, filtered, and evaporated in vacuo. The residue was triturated from diethylether and hexane and the solvents were evaporated in vacuo to provide N1-((1S,2R)-1-benzyl-3-(cyclopentyloxy)[(4-methoxyphenyl)sulfonyl]amino-2-hydroxypropyl)-2-methylbenzamide (27 mg, 89%) as a solid. H1-NMR (dimethylsulfoxide-D6): 1.75 (m, 8H), 1.87 (s, 3H), 2.63 (m, 1H), 2.79 (bm, 1H), 3.05 (bm, 1H), 3.21 (bm, 1H), 3.69 (bm, 1H), 3.86 (s, 3H), 4.13 (bm, 1H), 4.86 (bm, 1H), 5.28 (bs, 1H), 6.79 (m, 1H), 7.21 (m, 10H), 7.72 (d, 2H), 8.06 (d, 1H). MS(ESI): 575(M+Na).

Workup

  1. customthe reaction solvent was removed in vacuo
  2. customthe residue was purified on a preparative TLC plate (20×20 cm, 500 μM)
  3. washeluting with 96:4 methylene chloride
  4. customThe product band was removed
  5. washeluted with 4:1 methylene chloride
  6. filtrationmethanol, filtered
  7. customevaporated in vacuo
  8. customThe residue was triturated from diethylether and hexane
  9. customthe solvents were evaporated in vacuo

Sources & evidence

ORD record
ord-d950ddd320ca4e63a25573cca25af9f8
Source dataset
uspto-grants-2008_09
Patent number
US07419967B2

Reaction notes

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