Toluene → HCID 69116127, compound

HRID 1760543Notes

Reaction equation

HRID 1760543 reaction equation
C1(C)C=CC=CC=1.[H-].COCCO[Al+]OCCOC.[Na+].[H-].[C:22]([O:26][C:27](=[O:58])[NH:28][CH2:29][C:30]#[C:31][C:32]1[CH:33]=[C:34]2[C:39](=[CH:40][CH:41]=1)[N:38]=[CH:37][N:36]=[C:35]2[NH:42][C:43]1[CH:48]=[CH:47][C:46]([O:49][C:50]2[CH:51]=[N:52][C:53]([CH3:56])=[CH:54][CH:55]=2)=[C:45]([Cl:57])[CH:44]=1)([CH3:25])([CH3:24])[CH3:23]>O1CCCC1>[C:22]([O:26][C:27](=[O:58])[NH:28][CH2:29]/[CH:30]=[CH:31]/[C:32]1[CH:33]=[C:34]2[C:39](=[CH:40][CH:41]=1)[N:38]=[CH:37][N:36]=[C:35]2[NH:42][C:43]1[CH:48]=[CH:47][C:46]([O:49][C:50]2[CH:51]=[N:52][C:53]([CH3:56])=[CH:54][CH:55]=2)=[C:45]([Cl:57])[CH:44]=1)([CH3:25])([CH3:23])[CH3:24]

Participants

5

Reactant 3

HCID 1140TolueneHCID 21584525Sodium bis(2-methoxyethoxy)aluminiumhydrideHCID 69116126HCID 69116126, compound

Product 1

HCID 69116127HCID 69116127, compoundYield 88.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 7.53 mL of a 65% weight toluene solution of sodium bis(2-methoxyethoxy)aluminum hydride (Red-Al, 24.2 mmol) in 90 mL of tetrahydrofuran at 0° C. was added 5.0 g of (3-{4-[3-chloro-4-(6-methyl-pyridin-3-yloxy)-phenylamino]-quinazolin-6-yl}-prop-2-ynyl)-carbamic acid tert-butyl ester as a solid. The reaction was stirred at 0° C. for 2 hours, quenched with 10% aqueous potassium carbonate and extracted with ethyl acetate. The combined organics were dried and evaporated. The crude material was purified on 115 g of silica gel, eluting with 80% ethyl acetate/hexanes to afford 4.42 g of E-(3-{4-[3-chloro-4-(6-methyl-pyridin-3-yloxy)-phenylamino]-quinazolin-6-yl}-allyl)-carbamic acid tert-butyl ester. 1H NMR (CDCl3): δ 8.66 (s, 1), 8.24 (m, 1), 8.03 (m, 2), 7.77-7.65 (m, 3), 7.13 (m, 2), 6.97 (d, J=8.7 Hz, 1), 6.54 (d, 1), 6.35 (m, 1), 4.90 (m, 1) 3.90 (m, 2), 2.52 (s, 3), 1.46 (s, 9).

Workup

  1. customquenched with 10% aqueous potassium carbonate
  2. extractionextracted with ethyl acetate
  3. customThe combined organics were dried
  4. customevaporated
  5. customThe crude material was purified on 115 g of silica gel
  6. washeluting with 80% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-0769618733174c7399131c7b13ed6875
Source dataset
uspto-grants-2005_01
Patent number
US06844349B2

Reaction notes

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