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

HRID 2382052
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HRID 2382052 반응식
[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]
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참가 물질

7

반응물 3

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

생성물 1

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

시약·촉매·용매 3

HCID 887Methanol
용매
HCID 962Water용매
HCID 8857Ethyl Acetate용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-687b143eae9d43ce8b4ca6662f73b93d
출처 데이터셋
uspto-grants-2012_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08258130B2

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