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Triethylamine → 4-[4-(6-Fluoro-pyrido[3,4-d]pyrimidin-4-ylamino)-2-methyl-phenoxy]-piperidine-1-carboxylic acid (2,6-difluoro-phenyl)-amide

HRID 731906
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HRID 731906 반응식
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[N:9]=[C:10]=[O:11].Cl.[F:13][C:14]1[N:38]=[CH:37][C:17]2[N:18]=[CH:19][N:20]=[C:21]([NH:22][C:23]3[CH:28]=[CH:27][C:26]([O:29][CH:30]4[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]4)=[C:25]([CH3:36])[CH:24]=3)[C:16]=2[CH:15]=1.CCN(CC)CC>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[NH:9][C:10]([N:33]1[CH2:32][CH2:31][CH:30]([O:29][C:26]2[CH:27]=[CH:28][C:23]([NH:22][C:21]3[C:16]4[CH:15]=[C:14]([F:13])[N:38]=[CH:37][C:17]=4[N:18]=[CH:19][N:20]=3)=[CH:24][C:25]=2[CH3:36])[CH2:35][CH2:34]1)=[O:11]
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참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 5221622,6-Difluorophenyl isocyanateHCID 69056076(6-Fluoro-pyrido[3,4-d]pyrimidin-4-yl)-[3-methyl-4-(piperidin-4-yloxy)-phenyl]-amine hydrochloride

생성물 1

HCID 865952374-[4-(6-Fluoro-pyrido[3,4-d]pyrimidin-4-ylamino)-2-methyl-phenoxy]-piperidine-1-carboxylic acid (2,6-difluoro-phenyl)-amide수율 77%

시약·촉매·용매 1

HCID 6344
Dichloromethane
용매

실험 절차

2,6-difluorophenyl Isocyanate (0.199 g, 1.28 mmol) was added to a solution of (6-Fluoro-pyrido[3,4-d]pyrimidin-4-yl)-[3-methyl-4-(piperidin-4-yloxy)-phenyl]-amine hydrochloride (T) (500 mg, 1.28 mmol) and NEt3 (0.388 g, 3.84 mmol) in CH2Cl2 (20 mL). After 1 h the reaction was quenched with water, the layers were separated and the organic layer was washed with 1N NaOH and water, dried over Na2SO4, and concentrated. Purification by flash column chromatography (CH2Cl2/MeOH 97:3) afforded the title compound as a yellow solid (0.50 g, 77%). LRMS: 509.2 (MH+); 1H NMR (DMSO-d6, 400 MHz): δ 9.90 (s, 1H), δ 8.86 (s, 1H), δ 8.58 (s, 1H), δ 8.28 (s, 1H), δ 8.19 (s, 1H), δ 7.55-7.58 (m, 2H), δ 7.20-7.27 (m, 1H), δ 7.04-7.10 (m, 3H), δ 4.58-4.61 (m, 1H), δ 3.69-3.73 (m, 2H), δ 3.33-3.98 (m, 2H), δ 2.19 (s, 3H), δ 1.91-1.96 (m, 2H), δ 1.60-1.66 (m, 2H).

후처리

  1. customAfter 1 h the reaction was quenched with water
  2. customthe layers were separated
  3. washthe organic layer was washed with 1N NaOH and water
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customPurification by flash column chromatography (CH2Cl2/MeOH 97:3)

출처 및 근거

ORD 기록
ord-05d62207f9a84713b464931a28b2d383
출처 데이터셋
uspto-grants-2009_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07585869B2

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