tert-butyl N-(prop-2-yn-1-yl)carbamate → (3-{6-Amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl)-prop-2-ynyl)-carbamic acid tert-butyl ester

HRID 1627533Notes

Reaction equation

HRID 1627533 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([Cl:9])[C:3]=1[CH:10]([O:12][C:13]1[C:14]([NH2:20])=[N:15][CH:16]=[C:17](I)[CH:18]=1)[CH3:11].[C:21]([O:25][C:26](=[O:31])[NH:27][CH2:28][C:29]#[CH:30])([CH3:24])([CH3:23])[CH3:22]>C1COCC1.CCN(CC)CC.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:21]([O:25][C:26](=[O:31])[NH:27][CH2:28][C:29]#[C:30][C:17]1[CH:16]=[N:15][C:14]([NH2:20])=[C:13]([O:12][CH:10]([C:3]2[C:4]([Cl:9])=[CH:5][CH:6]=[C:7]([F:8])[C:2]=2[Cl:1])[CH3:11])[CH:18]=1)([CH3:24])([CH3:23])[CH3:22]

Participants

7

Reactant 2

HCID 11073648tert-butyl N-(prop-2-yn-1-yl)carbamateHCID 211113953-[1-(2,6-Dichloro-3-fluorophenyl)ethoxy]-5-iodopyridin-2-amine

Product 1

HCID 58885785(3-{6-Amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl)-prop-2-ynyl)-carbamic acid tert-butyl esterYield 29.2%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 3-[1-(2,6-Dichloro-3-fluoro-phenyl)-ethoxy]-5-iodo-pyridin-2-ylamine (7.1 g, 16.6 mmol) and prop-2-ynyl-carbamic acid tert-butyl ester (3.1 g, 20.0 mmol) in THF (60 mL) and Et3N (60 mL) was added CuI (63 mg, 0.3 mmol) and Pd(PPh3)4 (384 mg, 0.3 mmol). The mixture was stirred under nitrogen and monitored by TLC until the reaction was complete. The mixture was extracted with EtOAc and washed by water. The crude product was purified on a silica gel column eluting with 20-40% EtOAc in hexanes to provide (3-{6-Amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-prop-2-ynyl)-carbamic acid tert-butyl ester (2.2 g, 29% yield).

Workup

  1. extractionThe mixture was extracted with EtOAc
  2. washwashed by water
  3. customThe crude product was purified on a silica gel column
  4. washeluting with 20-40% EtOAc in hexanes

Sources & evidence

ORD record
ord-28e7256738174d7b8b2ebab777fde98d
Source dataset
uspto-grants-2014_07
Patent number
US08785632B2

Reaction notes

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