1,2-Dimethoxyethane → HCID 16123802, compound

HRID 886799Notes

Reaction equation

HRID 886799 reaction equation
Br[C:2]1[C:27](=[O:28])[N:26]([CH:29]([CH3:31])[CH3:30])[C:5]2[N:6]=[C:7]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([N:18]4[CH2:23][CH2:22][N:21]([CH2:24][CH3:25])[CH2:20][CH2:19]4)=[CH:14][CH:13]=3)[N:8]=[C:9]([CH3:10])[C:4]=2[CH:3]=1.[S:32]1[CH:36]=[CH:35][CH:34]=[C:33]1B(O)O.C(N(CC)CC)C.COCCOC>O>[CH2:24]([N:21]1[CH2:20][CH2:19][N:18]([C:15]2[CH:14]=[CH:13][C:12]([NH:11][C:7]3[N:8]=[C:9]([CH3:10])[C:4]4[CH:3]=[C:2]([C:33]5[S:32][CH:36]=[CH:35][CH:34]=5)[C:27](=[O:28])[N:26]([CH:29]([CH3:30])[CH3:31])[C:5]=4[N:6]=3)=[CH:17][CH:16]=2)[CH2:23][CH2:22]1)[CH3:25]

Participants

6

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 8471TriethylamineHCID 27339602-Thiopheneboronic acidHCID 16124011HCID 16124011, compound

Product 1

HCID 16123802HCID 16123802, compoundYield 7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
100 °C

Procedure

Pd(dppf) dichloromethane adduct (115 mg, 0.141 mmol) was added to a suspension of 6-bromo-2-{[4-(4-ethylpiperazin-1-yl)phenyl]amino}-4-methyl-8-(1-methylethyl)pyrido[2,3-d]pyrimidin-7(8H)-one (341 mg, 0.703 mmol), 2-thiophene boronic acid (99 mg, 0.77 mmol), and triethylamine (245 μL, 1.76 mmol) in 10:1 DME:water (6.6 mL). The reaction was heated to 100° C. After 24 h, the reaction was cooled to room temperature, diluted with water (50 mL) and filtered though a Celite plug and concentrated in vacuo. The residue was purified on reverse phase HPLC (25 mM ammonium acetate:acetonitrile, 30-80% gradient). The fractions containing product were collected and lyophilized to give 2-{[4-(4-Ethylpiperazin-1-yl)phenyl]amino}-4-methyl-8-(1-methylethyl)-6-(2-thienyl)pyrido[2,3-d]pyrimidin-7(8H)-one. (23 mg, 7% yield) as a yellow solid: 1H NMR (400 MHz, CDCl3): δ 8.08 (s, 1H), 7.63 (bd, J=3.2 Hz, 1H), 7.51 (m, 2H), 7.40 (bd, J=4.4 Hz, 1H), 7.11 (m, 2H), 6.97 (m, 2H), 5.90 (sept, 1H), 3.23 (m, 4H), 2.68 (s, 3H), 2.65 (m, 4H), 2.50 (q, J=7.2 Hz, 2H), 1.63 (d, J=6.8 Hz, 6H), 1.15 (t, J=7.2 Hz, 3H); MS (EI) for C27H32N6OS: 489.1 (MH+).

Workup

  1. temperaturethe reaction was cooled to room temperature
  2. filtrationfiltered though a Celite plug
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified on reverse phase HPLC (25 mM ammonium acetate:acetonitrile, 30-80% gradient)
  5. additionThe fractions containing product
  6. customwere collected

Sources & evidence

ORD record
ord-ea4e1003eff147c1a64d1b521fb22563
Source dataset
uspto-grants-2012_08
Patent number
US08247408B2

Reaction notes

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