Acetic Anhydride → HCID 10072170, compound

HRID 1948968Notes

Reaction equation

HRID 1948968 reaction equation
[C:1](OC(=O)C)(=[O:3])[CH3:2].Cl.[Cl:9][C:10]1[C:11]([F:36])=[C:12]([CH:33]=[CH:34][CH:35]=1)[NH:13][C:14]1[C:23]2[C:18](=[CH:19][C:20]([O:31][CH3:32])=[C:21]([O:24][C@H:25]3[CH2:30][CH2:29][CH2:28][NH:27][CH2:26]3)[CH:22]=2)[N:17]=[CH:16][N:15]=1.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[C:1]([N:27]1[CH2:28][CH2:29][CH2:30][C@H:25]([O:24][C:21]2[CH:22]=[C:23]3[C:18](=[CH:19][C:20]=2[O:31][CH3:32])[N:17]=[CH:16][N:15]=[C:14]3[NH:13][C:12]2[CH:33]=[CH:34][CH:35]=[C:10]([Cl:9])[C:11]=2[F:36])[CH2:26]1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 81531DiisopropylethylamineHCID 68521486HCID 68521486, compound

Product 1

HCID 10072170HCID 10072170, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of acetic anhydride (42 μl) in methylene chloride (5 ml) was added dropwise to a stirred solution of 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-[(3S)-piperidin-3-yloxy]quinazoline hydrochloride (0.175 g, 0.4 mmol; prepared as described in Example 49) and diisopropylethylamine (208 μl) in methylene chloride (20 ml) at 0° C. and the mixture was stirred for 2 hours and allowed to warm to room temperature. The reaction mixture was washed with saturated sodium bicarbonate solution, dried (MgSO4), filtered and evaporated to give a white foam. This was purified by column chromatography eluting with increasingly polar mixtures of methylene chloride/methanol (100/0 to 95/5). The fractions containing the desired product were combined and evaporated under vacuum to give the title product as a colourless foam (0.117 g, 66%); 1H NMR Spectrum: (DMSO d6 at 373K) 1.40-1.65 (m, 1H), 1.70-1.94 (m, 2H), 2.00 (s, 3H), 1.95-2.20 (m, 1H), 3.20-3.70 (m, 3H), 3.70-4.10 (m, 1H), 3.95 (s, 3H), 4.40-4.70 (m, 1H), 7.15-7.33 (m, 2H), 7.33-7.50 (m, 1H), 7.50-7.70 (m, 7.90 (s, 1H), 8.40 (s, 1H), 9.25 (s, 1H); Mass Spectrum: (M+H)+ 445.

Workup

  1. washThe reaction mixture was washed with saturated sodium bicarbonate solution
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. customevaporated
  5. customto give a white foam
  6. customThis was purified by column chromatography
  7. washeluting
  8. temperaturewith increasingly polar mixtures of methylene chloride/methanol (100/0 to 95/5)
  9. additionThe fractions containing the desired product
  10. customevaporated under vacuum

Sources & evidence

ORD record
ord-ea09550f5d724e3baf53199654d84a8c
Source dataset
uspto-grants-2013_03
Patent number
US08399667B2

Reaction notes

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