2-Mercaptoethanol → 4-{5-[3-({4-[(2-Hydroxyethyl)sulfanyl]pyrimidin-2-yl}amino)-5-methylphenyl]-1,3-thiazol-2-yl}-1,4-diazepan-2-one

HRID 1028137Notes

Reaction equation

HRID 1028137 reaction equation
C(=O)([O-])[O-].[K+].[K+].[SH:7][CH2:8][CH2:9][OH:10].[CH3:11][C:12]1[CH:13]=[C:14]([C:29]2[S:33][C:32]([N:34]3[CH2:40][CH2:39][CH2:38][NH:37][C:36](=[O:41])[CH2:35]3)=[N:31][CH:30]=2)[CH:15]=[C:16]([NH:18][C:19]2[N:24]=[C:23](S(C)(=O)=O)[CH:22]=[CH:21][N:20]=2)[CH:17]=1>CN(C=O)C.C(OCC)(=O)C>[OH:10][CH2:9][CH2:8][S:7][C:21]1[CH:22]=[CH:23][N:24]=[C:19]([NH:18][C:16]2[CH:15]=[C:14]([C:29]3[S:33][C:32]([N:34]4[CH2:40][CH2:39][CH2:38][NH:37][C:36](=[O:41])[CH2:35]4)=[N:31][CH:30]=3)[CH:13]=[C:12]([CH3:11])[CH:17]=2)[N:20]=1

Participants

6

Reactant 3

HCID 15672-MercaptoethanolHCID 11430Potassium CarbonateHCID 672408554-[5-(3-Methyl-5-{[4-(methylsulfonyl)-2-pyrimidinyl]amino}phenyl)-1,3-thiazol-2-yl]-1,4-diazepan-2-one

Product 1

HCID 710751514-{5-[3-({4-[(2-Hydroxyethyl)sulfanyl]pyrimidin-2-yl}amino)-5-methylphenyl]-1,3-thiazol-2-yl}-1,4-diazepan-2-oneYield 28.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Potassium carbonate (9.95 mg, 0.072 mmol) was added to a solution of 2-mercaptoethanol (18.34 μL, 0.262 mmol) stirring in DMF (327 μL) at room temperature in an oven-dried vial. Stirred for 15 minutes, then added 4-[5-(3-methyl-5-{[4-(methylsulfonyl)-2-pyrimidinyl]amino}phenyl)-1,3-thiazol-2-yl]-1,4-diazepan-2-one (30 mg, 0.065 mmol). Stirred at room temperature for 30 minutes, diluted with ethyl acetate (10 mL), and washed with 1:1 water:brine (10 mL). The organic extracts were dried (Na2SO4), filtered, and concentrated in vacuo. Purified by CombiFlash (100:0 to 0:20 dichloromethane:methanol) to afford 4-{5-[3-({4-[(2-hydroxyethyl)sulfanyl]pyrimidin-2-yl}amino)-5-methylphenyl]-1,3-thiazol-2-yl}-1,4-diazepan-2-one (8.4 mg, 0.018 mmol, 28.1% yield) as a yellow solid. MS APCI: [M+H]+ m/z 457.1. 1H NMR (500 MHz, DMSO) δ 9.52 (s, 1H), 8.14 (d, J=5.3 Hz, 1H), 7.58 (d, J=12.2 Hz, 2H), 7.47 (d, J=8.4 Hz, 2H), 6.92 (s, 1H), 6.75 (d, J=5.4 Hz, 1H), 4.97 (t, J=5.4 Hz, 1H), 4.16 (s, 2H), 3.79 (s, 2H), 3.64 (dd, J=6.3 Hz, 11.9 Hz, 2H), 3.29 (s, 1H), 3.21 (s, 2H), 3.15 (d, J=5.2 Hz, 1H), 2.27 (s, 3H), 1.78 (s, 2H). rhSYK activity=+++.

Workup

  1. stirringStirred at room temperature for 30 minutes
  2. washwashed with 1:1 water
  3. dry with materialThe organic extracts were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurified by CombiFlash (100:0 to 0:20 dichloromethane:methanol)

Sources & evidence

ORD record
ord-4c51e98a2203401bae3eedb0c48e7dda
Source dataset
uspto-grants-2014_05
Patent number
US08735417B2

Reaction notes

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