Tetrahydrofuran → HCID 66769738, compound

HRID 404774Notes

Reaction equation

HRID 404774 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]([CH2:21]Br)=[CH:17][C:18]([NH2:20])=O)[CH:10]=2)[CH:5]=[CH:6][CH:7]=1.C(N([CH2:28][CH3:29])CC)C.[C:30]([N:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1)([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31].[CH2:43]1[CH2:47][O:46][CH2:45][CH2:44]1>>[C:33]([O:32][C:30]([N:37]1[CH2:38][CH2:39][N:40]([CH2:47][CH:43]=[CH:44][C:45](=[O:46])[NH:20][C:18]2[CH:29]=[CH:28][CH:21]=[C:16]([NH:15][C:11]3[CH:10]=[C:9]([NH:8][C:4]4[CH:5]=[CH:6][CH:7]=[C:2]([CH3:1])[CH:3]=4)[N:14]=[CH:13][N:12]=3)[CH:17]=2)[CH2:41][CH2:42]1)=[O:31])([CH3:36])([CH3:35])[CH3:34]

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 8471TriethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 86630628HCID 86630628, compound

Product 1

HCID 66769738HCID 66769738, compound

Procedure

To a stirring solution at 0° C. under N2 of N-[3-(6-{3-methylphenyl}amino-pyrimidin-4-ylamino)-4-bromo-2-butenamide (Int-D) (2.15 g, 4.91 mmol) and triethylamine (0.86 mL, 6.17 mmol) in 10 mL of THF was added dropwise a solution of 1-Boc-piperazine (0.92 g, 4.91 mmol) in 10 mL of THF. The solution was allowed to warm to room temperature overnight, was concentrated and was then partitioned between EtOAc and sat. NaHCO3 solution. The organic extract was washed with brine solution, was dried (MgSO4), was filtered and was concentrated to give 2.76 g of 4-{3-[3-(6-{3-methylphenyl}amino-pyrimidin-4-ylamino)-phenylcarbamoyl]-allyl}-piperazine-1-carboxylic acid tert-butyl ester as gummy brown solid. This material was dissolved in 100 mL of CH2Cl2. 20 mL of trifluoroacetic acid was added and the mixture was stirred at room temperature under N2 for 2 h. The mixture was concentrated in vacuo, was basified with sat. NaHCO3 solution and was extracted with EtOAc (2×100 ml). The combined organic extract was dried (MgSO4), was filtered and was concentrated in vacuo. The residue was chromatographed (silica gel, 5% MeOH in CHCl3 [500 mL] then 1% NH4OH-10% MeOH in CHCl3) to give 0.404 g of (E)-N-3-(6-[3-methylphenyl]aminopyrimidin-4-yl)aminophenyl-4-piperazinyl-2-butenamide. (I-57) MS (m/z): 444 (M+1, 100%). 1H NMR (DMSO-d6) δ 10.03 (s, 1H), 9.17 (s, 1H), 9.07 (s, 1H), 8.27 (s, 1H), 7.90 (s, 1H), 7.17-7.36 (m, 6H), 6.79-6.80 (d, 1H), 6.72-6.75 (m, 1H), 6.29 (d, 1H), 6.20 (s, 1H), 3.08-3.39 (m, containing water and ˜3H), 2.70-2.72 (m, 4H), 2.30-2.42 (m, 4H), 2.29 (s, 3H.

Workup

  1. concentrationwas concentrated
  2. customwas then partitioned between EtOAc and sat. NaHCO3 solution
  3. extractionThe organic extract
  4. washwas washed with brine solution
  5. dry with materialwas dried (MgSO4)
  6. filtrationwas filtered
  7. concentrationwas concentrated

Sources & evidence

ORD record
ord-dfab11dcddbe45b68e299dbd89714f57
Source dataset
uspto-grants-2014_06
Patent number
US08748606B2

Reaction notes

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