Bis(2-oxo-3-oxazolidinyl)phosphinic chloride → 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-[2-(2-methoxy-ethoxy)-ethoxymethyl]-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide

HRID 33261Notes

Reaction equation

HRID 33261 reaction equation
[Cl:1][C:2]1[S:6][C:5]([C:7]2[O:11][N:10]=[C:9]([CH2:12][N:13]3[C:17]([CH2:18][O:19][CH2:20][CH2:21][O:22][CH2:23][CH2:24][O:25][CH3:26])=[CH:16][C:15]([C:27](O)=[O:28])=[N:14]3)[CH:8]=2)=[CH:4][CH:3]=1.Cl.[CH:31]([N:34]1[CH2:39][CH2:38][CH:37]([NH2:40])[CH2:36][CH2:35]1)([CH3:33])[CH3:32].C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1>C(Cl)Cl.CCN(CC)CC>[CH:31]([N:34]1[CH2:39][CH2:38][CH:37]([NH:40][C:27]([C:15]2[CH:16]=[C:17]([CH2:18][O:19][CH2:20][CH2:21][O:22][CH2:23][CH2:24][O:25][CH3:26])[N:13]([CH2:12][C:9]3[CH:8]=[C:7]([C:5]4[S:6][C:2]([Cl:1])=[CH:3][CH:4]=4)[O:11][N:10]=3)[N:14]=2)=[O:28])[CH2:36][CH2:35]1)([CH3:33])[CH3:32]

Participants

6

Reactant 3

HCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 230334601-Isopropylpiperidin-4-amine hydrochlorideHCID 574744121-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-[2-(2-methoxy-ethoxy)-ethoxymethyl]-1H-pyrazole-3-carboxylic acid

Product 1

HCID 670409111-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-[2-(2-methoxy-ethoxy)-ethoxymethyl]-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

To 60 mg 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-[2-(2-methoxy-ethoxy)-ethoxymethyl]-1H-pyrazole-3-carboxylic acid in 2 ml DCM and 0.1 ml NEt3, 30 mg 1-Isopropyl-piperidin-4-ylamine hydrochloride and 34 mg BOP-Cl were added at RT and the mixture was stirred for 16 h. The mixture was concentrated under reduced pressure and the residue was purified by preparative HPLC (C18 reverse phase column, elution with a H2O/MeCN gradient with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to yield a white solid. Yield: 19 mg MS (ES+): m/e=566, chloro pattern.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. customthe residue was purified by preparative HPLC (
  3. washC18 reverse phase column, elution with a H2O/MeCN gradient with 0.1% TFA)
  4. additionThe fractions containing the product
  5. customwere evaporated
  6. customto yield a white solid

Sources & evidence

ORD record
ord-359dcb679c854c3c8ab0699480da3fa1
Source dataset
uspto-grants-2008_09
Patent number
US07429581B2

Reaction notes

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