Acetic Acid → HCID 131731434, compound

HRID 402841Notes

Reaction equation

HRID 402841 reaction equation
[O:1]=[C:2]1[N:6]([C:7]2[CH:15]=[CH:14][C:10]([C:11]([OH:13])=[O:12])=[CH:9][CH:8]=2)[CH2:5][C:4]2([CH2:20][CH2:19][NH:18][CH2:17][CH2:16]2)[O:3]1.[Cl:21][C:22]1[CH:27]=[C:26]([CH:28]=O)[CH:25]=[C:24]([Cl:30])[C:23]=1[C:31]1[CH:36]=[CH:35][C:34]([F:37])=[CH:33][C:32]=1[F:38].C(O)(=O)C.C([BH3-])#N>CN(C=O)C>[ClH:21].[Cl:21][C:22]1[C:23]([C:31]2[CH:36]=[CH:35][C:34]([F:37])=[CH:33][C:32]=2[F:38])=[C:24]([Cl:30])[CH:25]=[C:26]([CH2:28][N:18]2[CH2:17][CH2:16][C:4]3([O:3][C:2](=[O:1])[N:6]([C:7]4[CH:8]=[CH:9][C:10]([C:11]([OH:13])=[O:12])=[CH:14][CH:15]=4)[CH2:5]3)[CH2:20][CH2:19]2)[CH:27]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 498716Cyano-borohydrideHCID 66764697HCID 66764697, compoundHCID 87139712HCID 87139712, compound

Product 1

HCID 131731434HCID 131731434, compoundYield 132.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-(2-oxo-1-oxa-3,8-diazaspiro[4.5]dec-3-yl)benzoic acid (27 mg, 0.087 mmol) (from Example 5-1, Step 4) and 2,6-dichloro-2′,4′-difluorobiphenyl-4-carboxaldehyde (20 mg, 0.070 mmol) (from Step 3) in DMF (2 mL) in a 20 mL scintillation vial was added acetic acid (13 uL, 0.209 mmol) and MP-cyanoborohydride resin (56 mg, 0.140 mmol, 2.49 mmol/g). The mixture was shaken at room temperature for 20 hours and then was filtered to remove the resin and washed with acetonitrile/water. The mixture was acidified with TFA and used directly for reverse phase (C-18) HPLC chromatography (10-55% acetonitrile/water gradient, 0.1% TFA) to afford the desired title compound (27 mg) as a solid TFA salt. The TFA salt was converted to the title compound hydrochloride salt by taking up in DCM and addition of excess 2M hydrogen chloride in ether and evaporation (twice) followed by trituration with ether to give the HCl salt (24 mg) as a white solid.

Workup

  1. filtrationwas filtered
  2. customto remove the resin
  3. washwashed with acetonitrile/water

Sources & evidence

ORD record
ord-ac03afe27d4640928e0d94ef92f2748c
Source dataset
uspto-grants-2014_06
Patent number
US08742110B2

Reaction notes

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