Triethylamine → N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)tetrahydrofuran-3-carboxamide

HRID 408268

반응식

HRID 408268 반응식
[Br:1][C:2]1[C:3]([F:12])=[C:4]2[C:10]([NH2:11])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[O:13]1[CH2:17][CH2:16][CH:15]([C:18](O)=[O:19])[CH2:14]1.C(N(CC)CC)C.C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1.O.[OH-].[Li+]>C(Cl)Cl.O>[Br:1][C:2]1[C:3]([F:12])=[C:4]2[C:10]([NH:11][C:18]([CH:15]3[CH2:16][CH2:17][O:13][CH2:14]3)=[O:19])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

참가 물질

8

반응물 5

HCID 8471TriethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 168937Lithium hydroxide, monohydrateHCID 4661317(R)-Tetrahydro-3-furoic acidHCID 602052765-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-amine

생성물 1

HCID 60205427N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)tetrahydrofuran-3-carboxamide수율 74%

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매

실험 절차

A mixture of 5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-amine (200 mg, 0.869 mmol, Example 1, Step H), tetrahydrofuran-3-carboxylic acid (202 mg, 1.74 mmol) and triethylamine (606 μL, 4.35 mmol) in CH2Cl2 (10 mL) at room temperature was treated with BOP-Cl (162 mg, 1.74 mmol). The mixture was stirred for 60 minutes, and the solvent was removed in vacuo. The resulting residue was dissolved in THF (10 mL) and treated with lithium hydroxide hydrate (109 mg, 2.61 mmol) in water (1 mL). After 30 minutes, the mixture was concentrated in vacuo, and water (5 mL) was added to the residue. The solid formed was filtered, washed with additional water and dried to provide N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)tetrahydrofuran-3-carboxamide (210 mg, 74% yield) as a solid. 1H NMR (400 MHz, (CD3)2SO) δ 12.07 (br s, 1H), 9.65 (s, 1H), 8.35 (d, 1H), 7.59 (s, 1H), 3.95 (t, 1H), 3.81-3.68 (m, 3H), 3.26-3.18 (m, 1H), 2.11-2.05 (m, 2H); LCMS (APCI+) m/z 327.9, 329.9 (M+H)+, Retention time=2.44 min (Method 2).

후처리

  1. customthe solvent was removed in vacuo
  2. dissolutionThe resulting residue was dissolved in THF (10 mL)
  3. waitAfter 30 minutes
  4. concentrationthe mixture was concentrated in vacuo, and water (5 mL)
  5. additionwas added to the residue
  6. customThe solid formed
  7. filtrationwas filtered
  8. washwashed with additional water
  9. customdried

출처 및 근거

ORD 기록
ord-824075a5dd32434db9d9262bb873f3dd
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08758830B2

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