Dimethylamine → 4-[6-(4-Dimethylcarbamoylmethyl-2-fluoro-phenoxy)-5-methyl-pyrimidin-4-yloxy]-piperidine-1-carboxylic Acid Isopropyl Ester

HRID 1174797노트

반응식

HRID 1174797 반응식
[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([CH3:20])=[C:18]([O:21][C:22]3[CH:27]=[CH:26][C:25]([CH2:28][C:29](O)=[O:30])=[CH:24][C:23]=3[F:32])[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].[CH3:33][N:34](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)[CH3:35].F[P-](F)(F)(F)(F)F.CNC>CN(C=O)C>[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([CH3:20])=[C:18]([O:21][C:22]3[CH:27]=[CH:26][C:25]([CH2:28][C:29](=[O:30])[N:34]([CH3:35])[CH3:33])=[CH:24][C:23]=3[F:32])[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2]

참가 물질

5

반응물 3

HCID 674DimethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 598566714-[6-(4-Carboxymethyl-2-fluoro-phenoxy)-5-methyl-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester

생성물 1

HCID 598568584-[6-(4-Dimethylcarbamoylmethyl-2-fluoro-phenoxy)-5-methyl-pyrimidin-4-yloxy]-piperidine-1-carboxylic Acid Isopropyl Ester수율 25.2%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A mixture of 4-[6-(4-carboxymethyl-2-fluoro-phenoxy)-5-methyl-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester (150 mg, 0.335 mmol) and HATU (178 mg, 0.469 mmol) in DMF (4 mL) was stirred for 30 minutes at room temperature. Then, dimethylamine (235 μL, 0.47 mmol) was added and the reaction was stirred for 24 hours at room temperature. The reaction was quenched with water and the product extracted in ethyl acetate. The organic layer was concentrated in vacuo and purified by HPLC to provide Compound C150 as a white solid (40 mg, 25%). 1H NMR (DMSO-d6, 400 MHz) δ 1.21 (d, 6H), 1.62-1.72 (m, 2H), 1.92-2.01 (m, 2H), 2.16 (s, 3H), 2.87 (s, 3H), 3.06 (s, 3H), 3.32-3.41 (m, 2H), 3.61-3.69 (m, 2H), 3.75 (s, 2H), 4.08 (h, 1H), 5.33 (h, 1H), 7.08 (d, 1H), 7.23-7.33 (m, 2H), 8.27 (s, 1H). Exact mass calculated for C24H31FN4O5 474.53, found 475.5 (MH+).

후처리

  1. stirringthe reaction was stirred for 24 hours at room temperature
  2. customThe reaction was quenched with water
  3. extractionthe product extracted in ethyl acetate
  4. concentrationThe organic layer was concentrated in vacuo
  5. custompurified by HPLC

출처 및 근거

ORD 기록
ord-58cd28f3939c495d8324192655c8868a
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07838525B2

반응 노트

불러오는 중…