Triethylamine → HCID 59175905, compound

HRID 1807740Notes

Reaction equation

HRID 1807740 reaction equation
[CH:1]1([CH2:4][NH:5][C:6](=[O:17])[NH:7][C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][CH:9]=2)[CH2:3][CH2:2]1.[F:18][C:19]([F:42])([F:41])[C:20]([C:26]1[CH:31]=[CH:30][C:29]([CH2:32][N:33]2[CH2:38][CH2:37][NH:36][CH2:35][C@@H:34]2[CH2:39][OH:40])=[CH:28][CH:27]=1)([OH:25])[C:21]([F:24])([F:23])[F:22].C(N(CC)CC)C.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>ClCCl>[CH:1]1([CH2:4][NH:5][C:6]([NH:7][C:8]2[CH:9]=[CH:10][C:11]([C:12]([N:36]3[CH2:37][CH2:38][N:33]([CH2:32][C:29]4[CH:30]=[CH:31][C:26]([C:20]([OH:25])([C:19]([F:18])([F:41])[F:42])[C:21]([F:24])([F:22])[F:23])=[CH:27][CH:28]=4)[C@@H:34]([CH2:39][OH:40])[CH2:35]3)=[O:14])=[CH:15][CH:16]=2)=[O:17])[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 580558194-(3-(Cyclopropylmethyl)ureido)benzoic acidHCID 86638556HCID 86638556, compound

Product 1

HCID 59175905HCID 59175905, compoundYield 35.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 4-(3-(cyclopropylmethyl)ureido)benzoic acid (0.487 mmol, 114 mg), (R)-1,1,1,3,3,3-hexafluoro-2-(4-((2-(hydroxymethyl)piperazin-1-yl)methyl)phenyl)propan-2-ol (0.443 mmol, 165 mg) and triethylamine (1.330 mmol, 0.185 mL, 135 mg) in dichloromethane (4 mL) was added 1-propanephosphonic acid cyclic anhydride (0.665 mmol, 0.395 mL, 423 mg, 50% solution in ethyl acetate). The reaction was stirred for 3 hours and then was diluted with dichloromethane/saturated sodium hydrogen carbonate (aqueous). The organic layer was separated, dried (magnesium sulfate) and concentrated under reduced pressure. The residue was purified by silica column chromatography (eluting with ethyl acetate to 5% methanol/ethyl acetate and basic reverse phase HPLC to afford the title compound (92 mg).

Workup

  1. customThe organic layer was separated
  2. dry with materialdried (magnesium sulfate)
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by silica column chromatography (
  5. washeluting with ethyl acetate to 5% methanol/ethyl acetate and basic reverse phase HPLC

Sources & evidence

ORD record
ord-6a6d124884644150965923324ca15516
Source dataset
uspto-grants-2013_01
Patent number
US08357679B2

Reaction notes

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