Methanol → N1-(3-Fluoro-4-(2-(3-hydroxyazetidine-1-carbonyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N3-(2-methoxyphenyl)malonamide

HRID 2193751Notes

Reaction equation

HRID 2193751 reaction equation
[Si]([O:8][CH:9]1[CH2:12][N:11]([C:13]([C:15]2[S:23][C:22]3[C:17](=[N:18][CH:19]=[CH:20][C:21]=3[O:24][C:25]3[CH:30]=[CH:29][C:28]([NH:31][C:32](=[O:45])[CH2:33][C:34]([NH:36][C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=4[O:43][CH3:44])=[O:35])=[CH:27][C:26]=3[F:46])[CH:16]=2)=[O:14])[CH2:10]1)(C(C)(C)C)(C)C.CO>>[F:46][C:26]1[CH:27]=[C:28]([NH:31][C:32](=[O:45])[CH2:33][C:34]([NH:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=2[O:43][CH3:44])=[O:35])[CH:29]=[CH:30][C:25]=1[O:24][C:21]1[CH:20]=[CH:19][N:18]=[C:17]2[CH:16]=[C:15]([C:13]([N:11]3[CH2:10][CH:9]([OH:8])[CH2:12]3)=[O:14])[S:23][C:22]=12

Participants

3

Reactant 2

HCID 887MethanolHCID 58790105N1-(4-(2-(3-(tert-Butyldimethylsilyloxy)azetidine-1-carbonyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N3-(2-methoxyphenyl)malonamide

Product 1

HCID 16041240N1-(3-Fluoro-4-(2-(3-hydroxyazetidine-1-carbonyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N3-(2-methoxyphenyl)malonamideYield 67.2%

Procedure

To a suspension of N1-(4-(2-(3-(tert-butyldimethylsilyloxy)azetidine-1-carbonyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N3-(2-methoxyphenyl) malonamide 275 (179 mg, 0.268 mmol) in MeOH (18 mL) HCl (1N in dioxane, 0.54 mL, 0.54 mmol) was added dropwise and the mixture was stirred for 15 min at room temperature. The solvent was removed under reduced pressure, MeOH was added to the residue and concentrated, the residue was suspended in water and lyophilized affording 271 (104.6 mg, 0.18 mmol, 67% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 10.68 (s, 1H), 9.64 (s, 1H), 8.64 (d. J=5.5 Hz, 1H), 8.06 (dd, J=1.9 Hz, J=9 Hz, 1H), 7.94 (s, 1H), 7.89 (dd, J=12.9 Hz, J=2.4 Hz, 1H), 7.51 (t, J=8.8 Hz, 1H), 7.46 (dd, J=1.6 Hz, J=8.8 Hz, 1H), 7.11-7.04 (m, 2H), 6.92 (m, 1H), 6.84 (dd, J=5.5 Hz, J=1 HZ, 1H), 6.90 (m, 1H), 4.59 (m, 1H), 4.36-4.31 (m, 2H), 3.88-3.84 (m, 4H), 3.67 (s, 2H). MS (m/z): (M+1) 551.0 (100%).

Workup

  1. additionwas added dropwise
  2. customThe solvent was removed under reduced pressure, MeOH
  3. additionwas added to the residue
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-4502f1881c2d45da8189f69c1835ad20
Source dataset
uspto-grants-2012_12
Patent number
US08329726B2

Reaction notes

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