Triethylamine → 5-(6-Hydroxymethyl-pyrimidin-4-yloxy)-2,3-dihydro-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

HRID 2264615Notes

Reaction equation

HRID 2264615 reaction equation
[F:1][C:2]([F:32])([F:31])[C:3]1[CH:4]=[C:5]([NH:9][C:10]([N:12]2[C:20]3[C:15](=[CH:16][C:17]([O:21][C:22]4[N:27]=[CH:26][N:25]=[C:24]([C:28](O)=[O:29])[CH:23]=4)=[CH:18][CH:19]=3)[CH2:14][CH2:13]2)=[O:11])[CH:6]=[CH:7][CH:8]=1.CCN(CC)CC.C(OC(Cl)=O)C(C)C.[BH4-].[Na+]>C1COCC1.O.CCOC(C)=O.Cl>[F:31][C:2]([F:1])([F:32])[C:3]1[CH:4]=[C:5]([NH:9][C:10]([N:12]2[C:20]3[C:15](=[CH:16][C:17]([O:21][C:22]4[CH:23]=[C:24]([CH2:28][OH:29])[N:25]=[CH:26][N:27]=4)=[CH:18][CH:19]=3)[CH2:14][CH2:13]2)=[O:11])[CH:6]=[CH:7][CH:8]=1

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 4311764Sodium borohydrideHCID 59596375HCID 59596375, compound

Product 1

HCID 595963475-(6-Hydroxymethyl-pyrimidin-4-yloxy)-2,3-dihydro-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To an ice-cooled solution of 400 mg (0.9 mMol) 6-[1-(3-trifluoromethyl-phenylcarbamoyl)-2,3-dihydro-1H-indol-5-yloxy]-pyrimidine-4-carboxylic acid (Expl. 73) in 12 ml THF are added 137 μl (0.99 mMol) Et3N and 130 μl (0.99 mMol) iso-butyl-chloroformate. After 1 h the resulting suspension is added dropwise to 75 mg (1.98 mMol) NaBH4 in 10 ml of water. After 30 min the mixture is diluted with EtOAc and 1 M HCl, the aqueous layer separeted off and extracted twice with EtOAc. The organic phases are washed with 1 M NaOH, water and brine, dried (Na2SO4) and concentrated. Chromatography (Combi Flash; hexane/EtOAc 1:1→1:9) gives the title compound: MS: [M+1]+=431; HPLC: AtRet=13.6.

Workup

  1. extractionextracted twice with EtOAc
  2. washThe organic phases are washed with 1 M NaOH, water and brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-b9b598d16e0746d599c6f7b735d6bb1e
Source dataset
uspto-grants-2010_12
Patent number
US07855215B2

Reaction notes

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