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 1766713Notes

Reaction equation

HRID 1766713 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.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

6

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 3

HCID 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 Cul (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-7c087e6b234e485189193cf38f8ad60d
Source dataset
uspto-grants-2007_06
Patent number
US07230098B2

Reaction notes

Loading…