Hydrochloric Acid → 1-(4-(2-(3-(2-Bromo-4-fluorophenoxy)-5-(3-methoxyphenylthio)pyridin-2-ylamino)thiazol-4-yl)piperidin-1-yl)ethanone hydrochloride

HRID 911918Notes

Reaction equation

HRID 911918 reaction equation
[Br:1][C:2]1[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:3]=1[O:4][C:5]1[C:6]([NH:20][C:21]2[S:22][CH:23]=[C:24]([CH:26]3[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]3)[N:25]=2)=[N:7][CH:8]=[C:9]([S:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=2)[CH:10]=1.C(N(CC)CC)C.[CH3:44][C:45](OC(C)=O)=[O:46].[ClH:51]>C(Cl)Cl>[ClH:51].[Br:1][C:2]1[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:3]=1[O:4][C:5]1[C:6]([NH:20][C:21]2[S:22][CH:23]=[C:24]([CH:26]3[CH2:31][CH2:30][N:29]([C:45](=[O:46])[CH3:44])[CH2:28][CH2:27]3)[N:25]=2)=[N:7][CH:8]=[C:9]([S:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=2)[CH:10]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 577426883-(2-bromo-4-fluorophenoxy)-5-(3-methoxyphenylthio)-N-(4-(piperidin-4-yl)thiazol-2-yl)pyridin-2-amine

Product 1

HCID 250997691-(4-(2-(3-(2-Bromo-4-fluorophenoxy)-5-(3-methoxyphenylthio)pyridin-2-ylamino)thiazol-4-yl)piperidin-1-yl)ethanone hydrochlorideYield 84.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A 20 mL vial was charged with 3-(2-bromo-4-fluorophenoxy)-5-(3-methoxyphenylthio)-N-(4-(piperidin-4-yl)thiazol-2-yl)pyridin-2-amine (40 mg, 0.068 mmol), triethylamine (0.0190 mL, 0.14 mmol), and CH2Cl2 (2 mL). Ac2O (0.008 mL, 0.082 mmol) was added and the reaction was stirred at room temperature for 10 minutes. The reaction was partitioned between CH2Cl2 and saturated aqueous sodium bicarbonate. The organic layer was dried with sodium sulfate, filtered and concentrated to afford the title compound (38.2 mg, 84.2% yield) as a white solid after HCl salt formation. 1H NMR (d6-DMSO) δ 11.20 (bs, 1H), 8.17 (d, 1H), 7.74 (m, 1H), 7.31 (m, 2H), 7.21 (t, 1H), 6.93 (d, 1H), 6.78 (m, 1H), 6.74 (s, 1H), 6.71 (m, 2H), 4.43 (d, 1H), 3.87 (d, 1H), 3.69 (s, 3H), 3.14 (m, 1H), 2.86 (m, 1H), 2.64 (m, 1H), 2.01 (s, 3H), 1.95 (m, 2H), 1.58 (m, 1H), 1.45 (m, 1H). Mass spectrum (apci) m/z=631.4 (M+H—HCl).

Workup

  1. customThe reaction was partitioned between CH2Cl2 and saturated aqueous sodium bicarbonate
  2. dry with materialThe organic layer was dried with sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-81d977b529224a5fb5d5a39a9a76a86d
Source dataset
uspto-grants-2011_09
Patent number
US08022223B2

Reaction notes

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