1,4'-Bipiperidine → (R)-2-Hydroxy-3-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)-1-(4-(piperidin-1-yl)piperidin-1-yl)propan-1-one

HRID 501943Notes

Reaction equation

HRID 501943 reaction equation
[OH:1][C@H:2]([CH2:6][C:7]1[CH:15]=[C:14]([CH3:16])[C:13]2[C:9](=[CH:10][N:11]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[N:12]=2)[CH:8]=1)[C:3]([OH:5])=O.C(N(C(C)C)CC)(C)C.[N:34]1([CH:40]2[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]2)[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C)C=O.ClCCl>[OH:1][C@H:2]([CH2:6][C:7]1[CH:15]=[C:14]([CH3:16])[C:13]2[C:9](=[CH:10][N:11]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:23])([CH3:22])[CH3:24])[N:12]=2)[CH:8]=1)[C:3]([N:43]1[CH2:44][CH2:45][CH:40]([N:34]2[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]2)[CH2:41][CH2:42]1)=[O:5]

Participants

7

Reactant 4

HCID 786071,4'-BipiperidineHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 59424393(R)-2-Hydroxy-3-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)propanoic acid

Product 1

HCID 59424402(R)-2-Hydroxy-3-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)-1-(4-(piperidin-1-yl)piperidin-1-yl)propan-1-one

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of the (R)-2-hydroxy-3-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)propanoic acid (610 mg, 1.74 mmol), diisopropylethylamine (0.61 mL, 3.48 mmol), and 4-piperidinopiperidine (585.76 mg, 2.0 equiv) in dimethylformamide (20 mL) and dichloromethane (20 mL) at 0° C. was added PyBOP® (951 mg, 1.83 mmol). The reaction was stirred at 0° C. for 2 h. The reaction was concentrated, diluted with ethyl acetate, washed with water, then brine, dried over magnesium sulfate, and concentrated. The product was purified by column chromatography (4:96:1 methanol/dichloromethane/triethylamine) to give 795 mg (91%). Mass spec.: 501.40 (MH)+.

Workup

  1. concentrationThe reaction was concentrated
  2. additiondiluted with ethyl acetate
  3. washwashed with water
  4. dry with materialbrine, dried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe product was purified by column chromatography (4:96:1 methanol/dichloromethane/triethylamine)
  7. customto give 795 mg (91%)

Sources & evidence

ORD record
ord-6c0706a70a59471a962d48c4427b558c
Source dataset
uspto-grants-2010_08
Patent number
US07772244B2

Reaction notes

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