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

HRID 911919Notes

Reaction equation

HRID 911919 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.[ClH:44].[CH3:45][N:46]([CH3:51])[CH2:47][C:48]([Cl:50])=[O:49].Cl>C(Cl)Cl>[ClH:50].[ClH:44].[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:48](=[O:49])[CH2:47][N:46]([CH3:51])[CH3:45])[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 8471TriethylamineHCID 139949912-(Dimethylamino)acetyl chloride hydrochlorideHCID 577426883-(2-bromo-4-fluorophenoxy)-5-(3-methoxyphenylthio)-N-(4-(piperidin-4-yl)thiazol-2-yl)pyridin-2-amine

Product 1

HCID 866315301-(4-(2-(3-(2-Bromo-4-fluorophenoxy)-5-(3-methoxyphenylthio)pyridin-2-ylamino)thiazol-4-yl)piperidin-1-yl)-2-(dimethylamino)ethanone dihydrochlorideYield 70.2%

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 (0.028 mL, 0.20 mmol), and CH2Cl2 (2 mL). 2-(Dimethylamino)acetyl chloride hydrochloride (12.9 mg, 0.0817 mmol) was added and 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. The residue was purified on silica gel (15% MeOH in EtOAc with 0.3% ammonia) to afford 1 the title compound (35.6 mg, 70.1% yield) after HCl salt formation. 1H NMR (d6-DMSO) δ 11.15 (bs, 1H), 9.60 (bs, 1H), 8.17 (d, 1H), 7.75 (m, 1H), 7.32 (m, 2H), 7.21 (t, 1H), 6.94 (d, 1H), 6.79 (m, 1H), 6.75 (s, 1H), 6.71 (m, 2H), 4.42 (d, 1H), 4.31 (qd, 2H), 3.69 (s, 3H), 3.19 (t, 1H), 2.93 (m, 1H), 2.82 (m, 6H), 2.04 (d, 2H), 1.64 (m, 1H), 1.52 (m, 1H). Mass spectrum (apci) m/z=674.3 (M+H-2HCl).

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
  5. customThe residue was purified on silica gel (15% MeOH in EtOAc with 0.3% ammonia)

Sources & evidence

ORD record
ord-a9bd45c01f714d46acdaa0af73afc145
Source dataset
uspto-grants-2011_09
Patent number
US08022223B2

Reaction notes

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