Lithium Hydroxide → N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-6-methoxypicolinamide

HRID 1923759Notes

Reaction equation

HRID 1923759 reaction equation
[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.[CH3:13][O:14][C:15]1[N:20]=[C:19]([C:21](O)=[O:22])[CH:18]=[CH:17][CH:16]=1.O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1.C(N(CC)CC)C.[Li+].[OH-]>C(Cl)Cl.O>[Br:1][C:2]1[C:3]([F:12])=[C:4]2[C:10]([NH:11][C:21](=[O:22])[C:19]3[CH:18]=[CH:17][CH:16]=[C:15]([O:14][CH3:13])[N:20]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

8

Reactant 5

HCID 3939Lithium HydroxideHCID 8471TriethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 5708916-Methoxypicolinic acidHCID 602052765-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-amine

Product 1

HCID 60205376N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-6-methoxypicolinamideYield 72.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-amine (200 mg, 0.869 mmol, Example 1, Step H) in CH2Cl2 (10 mL) was treated with 6-methoxypicolinic acid (160 mg, 1.04 mmol), bis(2-oxooxazolidin-3-yl)phosphinic chloride (332 mg, 1.30 mmol) and triethylamine (440 mg, 4.35 mmol). The reaction was stirred at room temperature for 1 hour, and then 2M aqueous LiOH (3 mL) was added. The reaction was stirred for 1 hour, and then water was added (10 mL). The solid, which separated, was filtered and washed with CH2Cl2 (10 mL). The filtered cake was dried to yield N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-6-methoxypicolinamide (229 mg, 72% yield). 1H NMR (400 MHz, (CD3)2SO) δ 12.17 (s, 1H), 12.25 (s, 1H), 8.40 (d, 1H), 7 96 (dd, 1H), 7.92 (dd. 1H), 7.74 (dd. 1H), 7.11 (dd, 1H), 4.05 (s, 3H); LCMS (APCI+) m/z 365, 366.9 (M+H)+, Retention time=3.75 minutes (Method 2).

Workup

  1. stirringThe reaction was stirred for 1 hour
  2. customThe solid, which separated
  3. filtrationwas filtered
  4. washwashed with CH2Cl2 (10 mL)
  5. customThe filtered cake was dried

Sources & evidence

ORD record
ord-a31d2bc841174d9985abd2e3a2aae2af
Source dataset
uspto-grants-2012_05
Patent number
US08178131B2

Reaction notes

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