Borane;tetrahydrofuran → HCID 86669376, compound

HRID 537357Notes

Reaction equation

HRID 537357 reaction equation
[C:1]([C:3]1([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=2[CH2:48][CH2:49][C:50](O)=[O:51])[CH2:8][CH2:7][N:6]([C:9]([C@:11]2([O:32][C:33]3[CH:37]=[C:36]([C:38]([F:41])([F:40])[F:39])[S:35][CH:34]=3)[CH2:16][CH2:15][CH2:14][N:13]([C:17](=[O:28])[C:18]3[C:23]([C:24]([F:27])([F:26])[F:25])=[CH:22][CH:21]=[N:20][CH:19]=3)[C@@H:12]2[CH2:29][CH2:30][CH3:31])=[O:10])[CH2:5][CH2:4]1)#[N:2].B.C1COCC1>C1COCC1>[OH:51][CH2:50][CH2:49][CH2:48][C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=1[C:3]1([C:1]#[N:2])[CH2:4][CH2:5][N:6]([C:9]([C@:11]2([O:32][C:33]3[CH:37]=[C:36]([C:38]([F:41])([F:39])[F:40])[S:35][CH:34]=3)[CH2:16][CH2:15][CH2:14][N:13]([C:17](=[O:28])[C:18]3[C:23]([C:24]([F:25])([F:26])[F:27])=[CH:22][CH:21]=[N:20][CH:19]=3)[C@@H:12]2[CH2:29][CH2:30][CH3:31])=[O:10])[CH2:7][CH2:8]1

Participants

4

Reactant 2

HCID 2723981Borane;tetrahydrofuranHCID 86669377HCID 86669377, compound

Product 1

HCID 86669376HCID 86669376, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Acid A136 3-(2-(4-cyano-1-((2R,3S)-2-propyl-1-(4-(trifluoromethyl)nicotinoyl)-3-(5-(trifluoromethyl)thiophen-3-yloxy)piperidine-3-carbonyl)piperidin-4-yl)phenyl)propanoic acid (10 mg, 13.3 μmol) was dissolved in THF (0.5 mL). The mixture was cooled to 0° C. and BH3.THF (30 μL, 27.9 μmol) was added dropwise under Ar. The reaction was warmed to 23° C. and was stirred overnight. The reaction mixture was quenched with 1 M NaOH and was concentrated. The crude residue was purified by reverse phase preparative HPLC to yield 4-(2-(3-hydroxypropyl)phenyl)-1-((2R,3S)-2-propyl-1-(4-(trifluoromethyl)nicotinoyl)-3-(5-(trifluoromethyl)thiophen-3-yloxy)piperidine-3-carbonyl)piperidine-4-carbonitrile A138. LC/MS RT (10 min method)=6.04 min. Mass observed: 737.25 (M+H).

Workup

  1. temperatureThe reaction was warmed to 23° C.
  2. customThe reaction mixture was quenched with 1 M NaOH
  3. concentrationwas concentrated
  4. customThe crude residue was purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-2081d37117f04d0aaaecae64326bb007
Source dataset
uspto-grants-2014_10
Patent number
US08859776B2

Reaction notes

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