1,2-Dichloroethane → Tert-butyl (2R,5S)-2-[(R)-hydroxy(pyridin-3-yl)methyl]-5-(4-{[5-(1H-pyrazol-1-yl)piperidin-1-yl]carbonyl}benzyl)pyrrolidine-1-carboxylate

HRID 1804646

Reaction equation

HRID 1804646 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@@H:12]([C@H:13]([OH:20])[C:14]2[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=2)[CH2:11][CH2:10][C@H:9]1[CH2:21][C:22]1[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][CH:23]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N:31]1([CH:36]2[CH2:41][CH2:40]NC[CH2:37]2)[CH:35]=[CH:34][CH:33]=[N:32]1.C1C=[N:46][C:45]2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C>CN(C=O)C>[OH:20][C@H:13]([C:14]1[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=1)[C@H:12]1[CH2:11][CH2:10][C@@H:9]([CH2:21][C:22]2[CH:23]=[CH:24][C:25]([C:26]([N:46]3[CH2:37][CH:36]([N:31]4[CH:35]=[CH:34][CH:33]=[N:32]4)[CH2:41][CH2:40][CH2:45]3)=[O:27])=[CH:29][CH:30]=2)[N:8]1[C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 211930454-(1H-Pyrazol-1-yl)piperidineHCID 679723824-({(2S,5R)-1-(tert-butoxycarbonyl)-5-[(R)-hydroxy(pyridin-3-yl)methyl]pyrrolidin-2-yl}methyl)benzoic acid

Product 1

HCID 86666755Tert-butyl (2R,5S)-2-[(R)-hydroxy(pyridin-3-yl)methyl]-5-(4-{[5-(1H-pyrazol-1-yl)piperidin-1-yl]carbonyl}benzyl)pyrrolidine-1-carboxylateYield 75%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 4-{((2S,5R)-1-(tert-butoxycarbonyl)-5-[(R)-hydroxy(pyridin-3-yl)methyl]pyrrolidin-2-yl)methyl}benzoic acid (i-4, 40 mg, 0.1 mmol) and 4-(1H-pyrazol-1-yl)piperidine (15 mg, 0.1 mmol) in 1.0 mL anhydrous DMF was added a 0.5 M solution of HOAt in DMF (0.2 mL, 0.1 mmol) followed by EDC (40 mg, 0.2 mmol) and DIEA (35 μL, 0.2 mmol). The resulting mixture was stirred at RT under nitrogen atmosphere for 16 h. The mixture was washed with water and extracted with dichloromethane (2×5 mL). The organics were combined, dried over sodium sulfate, filtered and concentrated in vacuum. The residue was purified by preparative TLC plate (1000 uM) eluting with 10% MeOH in dichloromethane to afford the title compound (38 mg, 75%). ESI-MS calculated for C31H39N5O4: Exact Mass: 545.30. Found 546.30 (MH)+ and 568.28 (MNa)+.

Workup

  1. washThe mixture was washed with water
  2. extractionextracted with dichloromethane (2×5 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuum
  6. customThe residue was purified by preparative TLC plate (1000 uM)
  7. washeluting with 10% MeOH in dichloromethane

Sources & evidence

ORD record
ord-e9693ae8171a4d0b8c3df7afbf0f532e
Source dataset
uspto-grants-2013_01
Patent number
US08354403B2

Linked notes

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