Hydrochloric Acid → 4-Methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid (5-fluoro-3-hydroxymethyl-indol-1-yl)-amide

HRID 2382052Notes

Reaction equation

HRID 2382052 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([NH:11][C:12]([C:14]1[C:15]([CH3:26])=[N:16][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=3)=[N:18][CH:19]=1)=[O:13])[CH:6]=[C:5]2[CH:27]=[O:28].[BH4-].[Na+].Cl>CO.CCOC(C)=O.O>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([NH:11][C:12]([C:14]1[C:15]([CH3:26])=[N:16][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=3)=[N:18][CH:19]=1)=[O:13])[CH:6]=[C:5]2[CH2:27][OH:28]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 592000434-Methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid (5-fluoro-3-formyl-indol-1-yl)-amide

Product 1

HCID 591999504-Methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid (5-fluoro-3-hydroxymethyl-indol-1-yl)-amideYield 38.8%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 4-methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid (5-fluoro-3-formyl-indol-1-yl)-amide (230 mg, 0.614 mmol) in MeOH (10 mL) is treated with NaBH4 (233 mg, 6.14 mmol) and stirred at rt for 1 h. The mixture is diluted with EtOAc (50 mL) and H2O, neutralized with HCl (conc.), and extracted with EtOAc (3×50 mL). The combined organic layer is dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by preparative reverse-phase HPLC eluting with 20%-100% MeCN in H2O to afford 4-methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid (5-fluoro-3-hydroxymethyl-indol-1-yl)-amide (90 mg, 8%). MS: 378 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 11.92 (s, NH, 1H), 9.27 (s, 1H), 8.81 (d, 1H), 8.47 (d, 1H), 8.05 (m, 1H), 7.61 (m, 1H), 7.44 (m, 3H), 7.10 (m, 1H), 5.00 (t, OH, 1H), 4.66 (d, 2H), 2.78 (s, 3H).

Workup

  1. extractionextracted with EtOAc (3×50 mL)
  2. dry with materialThe combined organic layer is dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue is purified by preparative reverse-phase HPLC
  6. washeluting with 20%-100% MeCN in H2O

Sources & evidence

ORD record
ord-687b143eae9d43ce8b4ca6662f73b93d
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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