Sodium Iodide → HCID 11467476, compound

HRID 748626Notes

Reaction equation

HRID 748626 reaction equation
Br[CH2:2]/[CH:3]=[CH:4]/[C:5](Cl)=[O:6].[NH2:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][C:18]=1[O:19][CH3:20])[N:15]=[CH:14][C:13]([C:21]#[N:22])=[C:12]2[NH:23][C:24]1[CH:29]=[CH:28][C:27]([S:30][C:31]2[S:32][CH:33]=[CH:34][N:35]=2)=[C:26]([Cl:36])[CH:25]=1.[CH3:37][O:38][CH2:39][CH2:40][NH:41][CH3:42].[I-].[Na+]>C1COCC1>[Cl:36][C:26]1[CH:25]=[C:24]([CH:29]=[CH:28][C:27]=1[S:30][C:31]1[S:32][CH:33]=[CH:34][N:35]=1)[NH:23][C:12]1[C:11]2[C:16](=[CH:17][C:18]([O:19][CH3:20])=[C:9]([NH:8][C:5](=[O:6])/[CH:4]=[CH:3]/[CH2:2][N:41]([CH2:40][CH2:39][O:38][CH3:37])[CH3:42])[CH:10]=2)[N:15]=[CH:14][C:13]=1[C:21]#[N:22]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 300977(2-Methoxyethyl)(methyl)amineHCID 10225237HCID 10225237, compoundHCID 11263885(E)-4-Bromo-2-butenoyl Chloride

Product 1

HCID 11467476HCID 11467476, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

(E)-N-{4-[3-chloro-4-(1,3-thiazol-2-ylsulfanyl)anilino]-3-cyano-7-methoxy-6-quinolinyl}-4-[(2-methoxyethyl)(methyl)amino]-2-butenamide was prepared by adding dropwise, 3.43 g (18.71 mmol, 1.95 mL) 4-bromocrotonyl chloride in 12 mL THF over 45 minutes to a stirred solution of 4.7 g (10.69 mmol) 6-amino-4-[3-chloro-4-(thiazol-2-ylsulfanyl)-phenylamino]-7-methoxy-quinolin-3-carbonitrile in 588 mL THF containing 3.73 mL (21.36 mmol) diisopropylethylamine, at 0° C. under nitrogen. The reaction produced a mixture of 4-bromo-(and chloro)-but-2-enoic acid {4-[3-chloro-4-(thiazol-2-ylsulfanyl)-phenylamino]-3-cyano-7-methoxy-quinolin-6-yl}-amide. A 300 mL portion of the solution was cooled to 0° C. and 2.38 g (26.7 mmol) (2-methoxyethyl)-methylamine in 11 mL THF was added dropwise. After the reaction had warmed to room temperature, 401 mg (0.5 eq) of sodium iodide was added and the solution was stirred overnight. The solvents were evaporated to leave a red gum, which was partitioned between EtOAc and saturated NaHCO3. After standing overnight, the layers were separated and the organic layer was dried and evaporated. Chromatography of the residue on a short column of Kieselgel 60, eluting with EtOAc, then EtOAc/15% MeOH, and finally EtOAc/15% MeOH/1% Et3N yielded 1.3 g (41%) of the product as a yellow glass; HRMS (ESI) m/z 595.13338 (M)+1, Δ=−2.28 mmu.

Workup

  1. additionby adding dropwise
  2. customat 0° C.
  3. customThe reaction produced
  4. temperatureAfter the reaction had warmed to room temperature
  5. customThe solvents were evaporated
  6. customto leave a red gum, which
  7. customwas partitioned between EtOAc and saturated NaHCO3
  8. waitAfter standing overnight
  9. customthe layers were separated
  10. customthe organic layer was dried
  11. customevaporated
  12. washChromatography of the residue on a short column of Kieselgel 60, eluting with EtOAc

Sources & evidence

ORD record
ord-96c8f257c9c04c169c2626e805372e12
Source dataset
uspto-grants-2008_07
Patent number
US07399865B2

Reaction notes

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