Diisopropylethylamine → HCID 20664172, compound

HRID 1068207Notes

Reaction equation

HRID 1068207 reaction equation
C(N(C(C)C)CC)(C)C.FC(F)(F)C(O)=O.[CH2:17]([C:24]1[CH:28]=[C:27]([CH:29]2[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)[N:26]([CH2:35][CH3:36])[N:25]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[CH:37]([C@@H:39]1[C@@H:43]([C:44]2[CH:49]=[CH:48][CH:47]=[C:46]([F:50])[CH:45]=2)[CH2:42][N:41]([C@@H:51]2[C:55]([CH3:57])([CH3:56])[CH2:54][O:53][C:52]2=[O:58])[CH2:40]1)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH2:17]([C:24]1[CH:28]=[C:27]([CH:29]2[CH2:34][CH2:33][N:32]([CH2:37][C@@H:39]3[C@@H:43]([C:44]4[CH:49]=[CH:48][CH:47]=[C:46]([F:50])[CH:45]=4)[CH2:42][N:41]([C@@H:51]4[C:55]([CH3:57])([CH3:56])[CH2:54][O:53][C:52]4=[O:58])[CH2:40]3)[CH2:31][CH2:30]2)[N:26]([CH2:35][CH3:36])[N:25]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 20664169HCID 20664169, compoundHCID 21193074HCID 21193074, compound

Product 1

HCID 20664172HCID 20664172, compoundYield 37.5%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent3×

Procedure

Diisopropylethylamine (0.018 mL, 0.1 mmol) was added to a solution of 4-(3-benzyl-1-ethyl-(1H-pyrazol-5-yl))piperidine trifluoroacetate (37 mg, 0.1 mmol, from Example 1, Step C) in 0.5 mL of 1,2-dichloroethane (DCE). A solution of dihydro-3-(R)-(3-(R)-formyl-4-(S)-(3-fluorophenyl)-pyrrolidin-1-yl)-4,4-dimethyl-2(3H)furanone (25 mg, 0.082 mmol, from Step D) in 0.5 mL of DCE was then added, followed by a slurry of sodium triacetoxyborohydride (30 mg, 0.144 mmol) in 0.5 mL of DCE. The reaction mixture was mixed well, then allowed to stand at room temperature for 2 h. The mixture was concentrated and purified by preparative HPLC (column: YMC combiprep ODS-A 20×50 mm, gradient: 10% acetonitrile/water w/0.1% TFA to 100% acetonitrile/water w/0.1% TFA over 8 min, then ramp to 10% acetonitrile/water w/0.1% TFA over 2 min, flow: 20 mL/min), followed by conversion to the free base by solid phase extraction (column: Varian SCX, loading: methanol, elution: 2.0M ammonia in methanol) to afford 17.2 mg (37% yield) of the title compound. ESI-MS. M/z; (M+H)=559.7; HPLC A: 2.34 min.

Workup

  1. additionThe reaction mixture was mixed well
  2. concentrationThe mixture was concentrated
  3. custompurified by preparative HPLC (column
  4. customover 8 min
  5. customover 2 min
  6. extractionflow: 20 mL/min), followed by conversion to the free base by solid phase extraction (column: Varian SCX, loading: methanol, elution: 2.0M ammonia in methanol)

Sources & evidence

ORD record
ord-bbb4c18cbeb248b7a92b3825356387b8
Source dataset
uspto-grants-2001_06
Patent number
US06248755B1

Reaction notes

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