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

HRID 1028136Notes

Reaction equation

HRID 1028136 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH2:11]([SH:15])[CH2:12][CH2:13][CH3:14].[CH3:16][C:17]1[CH:18]=[C:19]([C:34]2[S:38][C:37]([N:39]3[CH2:45][CH2:44][CH2:43][NH:42][C:41](=[O:46])[CH2:40]3)=[N:36][CH:35]=2)[CH:20]=[C:21]([NH:23][C:24]2[N:29]=[C:28](S(C)(=O)=O)[CH:27]=[CH:26][N:25]=2)[CH:22]=1>CN(C=O)C.C(OCC)(=O)C>[CH2:11]([S:15][C:26]1[CH:27]=[CH:28][N:29]=[C:24]([NH:23][C:21]2[CH:20]=[C:19]([C:34]3[S:38][C:37]([N:39]4[CH2:45][CH2:44][CH2:43][NH:42][C:41](=[O:46])[CH2:40]4)=[N:36][CH:35]=3)[CH:18]=[C:17]([CH3:16])[CH:22]=2)[N:25]=1)[CH2:12][CH2:13][CH3:14]

Participants

6

Reactant 3

HCID 8012ButanethiolHCID 2724254Sodium bis(trimethylsilyl)amideHCID 672408554-[5-(3-Methyl-5-{[4-(methylsulfonyl)-2-pyrimidinyl]amino}phenyl)-1,3-thiazol-2-yl]-1,4-diazepan-2-one

Product 1

HCID 532513944-[5-(3-{[4-(Butylsulfanyl)pyrimidin-2-yl]amino}-5-methylphenyl)-1,3-thiazol-2-yl]-1,4-diazepan-2-oneYield 48%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Sodium bis(trimethylsilyl)amide (164 μL, 1.0 M, 0.164 mmol) was added to a solution of 1-butanethiol (28.1 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-(butylsulfanyl)pyrimidin-2-yl]amino}-5-methylphenyl)-1,3-thiazol-2-yl]-1,4-diazepan-2-one (14.6 mg, 0.031 mmol, 48% yield) as a white solid. MS APCI: [M+H]+ m/z 469.2. 1H NMR (500 MHz, DMSO) δ 9.52 (s, 1H), 8.13 (d, J=5.3 Hz, 1H), 7.60 (dd, J=4.9 Hz, 10.3 Hz, 2H), 7.45 (s, 1H), 7.43 (s, 1H), 6.92 (s, 1H), 6.72 (d, J=5.3 Hz, 1H), 4.16 (s, 2H), 3.84-3.73 (m, 2H), 3.25-3.12 (m, 4H), 2.26 (s, 3H), 1.78 (m, 2H), 1.59 (m, 2H), 1.35 (dd, J=7.4 Hz, 14.9 Hz, 2H), 0.83 (t, J=7.4 Hz, 3H).

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-25f5e88bf2ee4c1c8d193bf30ddc5ebb
Source dataset
uspto-grants-2014_05
Patent number
US08735417B2

Reaction notes

Loading…