Dimethylformamide → HCID 86664045, compound

HRID 712337Notes

Reaction equation

HRID 712337 reaction equation
[Li]CCCC.Br[C:7]1[C:15]2[S:14][C:13]([N:16]3[CH2:21][N:20]([CH3:22])[CH2:19][N:18]([CH2:23][CH3:24])[C:17]3=[O:25])=[N:12][C:11]=2[CH:10]=[C:9]([C:26]2[CH:27]=[N:28][C:29]([N:32]3[CH2:37][CH2:36][C:35]([CH2:43][CH3:44])([C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH2:34][CH2:33]3)=[N:30][CH:31]=2)[CH:8]=1.CN([CH:48]=[O:49])C>C1COCC1>[CH2:43]([C:35]1([C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH2:36][CH2:37][N:32]([C:29]2[N:28]=[CH:27][C:26]([C:9]3[CH:8]=[C:7]([CH:48]=[O:49])[C:15]4[S:14][C:13]([N:16]5[CH2:21][N:20]([CH3:22])[CH2:19][N:18]([CH2:23][CH3:24])[C:17]5=[O:25])=[N:12][C:11]=4[CH:10]=3)=[CH:31][N:30]=2)[CH2:33][CH2:34]1)[CH3:44]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 66977160HCID 66977160, compoundHCID 178418339Butyllithium

Product 1

HCID 86664045HCID 86664045, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1.4M BuLi (600 μL, 0.84 mmol) was added to ethyl 1-[5-[7-bromo-2-(3-ethyl-5-methyl-2-oxo-1,3,5-triazinan-1-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-ethyl-piperidine-4-carboxylate (250 mg, 0.41 mmol) in THF (10 mL) at −90° C. and the reaction stirred for 10 mins before DMF (300 μL) was added and the mixture stirred for a further 20 mins. The reaction was quenched with sat. NH4Cl (aq) then allowed to warm to rt before extraction with EtOAc (3×). Combined EtOAc extracts were dried and the solvent evaporated to yield the crude product which was purified by flash chromatography on 12 g SiO2 using EtOAc/Cyclohexane gradient 0-0% 3CV, 0-100% 20CV, 100-100% 5CV to yield the desired product (105 mg, 46%). 1H NMR (CDCl3) δ 10.22 (s, 1H), 8.63 (s, 2H), 8.06 (d, J=1.7 Hz, 1H), 7.83 (d, J=1.7 Hz, 1H), 5.21 (s, 2H), 4.56 (dt, J=13.8, 3.5 Hz, 2H), 4.33 (s, 2H), 4.23 (q, J=7.1 Hz, 2H), 3.51 (q, J=7.2 Hz, 2H), 3.23-3.13 (m, 2H), 2.67 (s, 3H), 2.25 (bd, J=13.4 Hz, 2H), 1.61 (q, J=7.6 Hz, 2H), 1.45 (ddd, J=13.5, 11.9, 4.2 Hz, 2H), 1.30 (t, J=7.1 Hz, 3H), 1.25 (t, J=7.2 Hz, 3H), 0.86 (t, J=7.5 Hz, 3H).

Workup

  1. additionwas added
  2. customThe reaction was quenched with sat. NH4Cl (aq)
  3. dry with materialCombined EtOAc extracts were dried
  4. customthe solvent evaporated
  5. customto yield the crude product which
  6. customwas purified by flash chromatography on 12 g SiO2

Sources & evidence

ORD record
ord-7e5075a2872a4b74a26bae069fe3a3cb
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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