Triethylamine → HCID 20664090, compound

HRID 1068200Notes

Reaction equation

HRID 1068200 reaction equation
[CH:1]([C@@H:3]1[C@@H:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([F:14])[CH:9]=2)[CH2:6][N:5]([C@H:15]([CH2:26][C:27]([CH3:30])([CH3:29])[CH3:28])[C:16]([O:18]CC2C=CC=CC=2)=[O:17])[CH2:4]1)=O.[H][H].Cl.[CH2:34]([C:41]1[CH:42]=[N:43][N:44]([CH2:52][CH3:53])[C:45]=1[CH:46]1[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CC(OC(OC(OC(C)(C)C)=O)=O)(C)C>CO.[Pd]>[CH2:34]([C:41]1[CH:42]=[N:43][N:44]([CH2:52][CH3:53])[C:45]=1[CH:46]1[CH2:51][CH2:50][N:49]([CH2:1][C@@H:3]2[C@@H:7]([C:8]3[CH:13]=[CH:12][CH:11]=[C:10]([F:14])[CH:9]=3)[CH2:6][N:5]([C@H:15]([CH2:26][C:27]([CH3:28])([CH3:30])[CH3:29])[C:16]([OH:18])=[O:17])[CH2:4]2)[CH2:48][CH2:47]1)[C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1

Participants

9

Reactant 6

HCID 8471TriethylamineHCID 90495Di-tert-butyl dicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 70125262HCID 70125262, compoundHCID 131722699HCID 131722699, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 20664090HCID 20664090, compoundYield 37.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A solution of 2-(R)-(3-(R)-Formyl-4-(S)-(3-fluorophenyl) pyrrolidin-1-yl)-4,4-dimethylpentanoic acid, benzyl ester (27 mg, 0.065 mmol, from Step B) in 2 mL methanol was stirred over 20 mg 10% Pd/C under 1 atm of hydrogen. After 1 h the mixture was filtered and concentrated. The crude material was dissolved in 2 mL DCE and 4-(4-Benzyl-1-ethyl-(1H-pyrazol-5-yl))-piperidine HCl (26 mg, 0.085 mmol, from EXAMPLE 8 Step F), triethylamine (21 μL, 0.15 mmol) and sodium triacetoxyborohydride (32 mg, 0.15 mmol) were added. The solution was stirred overnight then Boc anhydride (19 mg, 0.085 mmol) was added and stirring was continued for 3 h. The mixture was concentrated and the product was purified by flash chromatography (95/5 DCM/MeOH→95/5/0.5 DCM/MeOH/NH4OH) to afford 14 mg (37%) of the title compound. 1H NMR (500 MHz, CDCl3). δ1.03 (s, 9H), 1.31-1.34 (t, 3H), 1.36-1.45 (m, 1H), 1.5-1.59 (m, 1H), 1.64-1.72 (m, 2H), 1.76-1.8 (d, 1H), 1.91-2.0 (m, 2H), 2.08-2.13 (t, 1H), 2.37-2.4 (dd, 1H), 2.46-2.6 (m, 2H), 2.77-2.8 (m, 2HO, 2.96-3.0 (d, 1H), 3.18-3.37 (m, 2H), 3.56-3.6 (d, 1H), 3.7-3.82 (m, 2H), 3.85 (s, 2H), 4.01-4.05 (q, 2H), 5.72 (s, 1H), 6.97-7.0 (t, 1H), 7.13-7.2 (m, 5H), 7.22-7.28 (m, 2H), 7.33-7.4 (m, 1H). ESI-MS, M/z; (M+H)=575.6 (obs), 575.37 (calc.).

Workup

  1. filtrationAfter 1 h the mixture was filtered
  2. concentrationconcentrated
  3. dissolutionThe crude material was dissolved in 2 mL DCE
  4. stirringstirring
  5. waitwas continued for 3 h
  6. concentrationThe mixture was concentrated
  7. customthe product was purified by flash chromatography (95/5 DCM/MeOH→95/5/0.5 DCM/MeOH/NH4OH)

Sources & evidence

ORD record
ord-f5480934dfca451ca553f21891d55301
Source dataset
uspto-grants-2001_06
Patent number
US06248755B1

Reaction notes

Loading…