Butyl vinyl ether → tert-Butyl 4-(6-((6-(1-Butoxyethenyl)-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido(2,3-d)pyrimidin-2-yl)amino)-pyridin-3-yl)-piperazine-1-carboxylate

HRID 249706Notes

Reaction equation

HRID 249706 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:15]=[N:16][C:17]([NH:20][C:21]3[N:22]=[CH:23][C:24]4[C:30]([CH3:31])=[C:29]([C:32]([O:34][CH2:35][CH3:36])=[CH2:33])[C:28](=[O:37])[N:27]([CH:38]5[CH2:42][CH2:41][CH2:40][CH2:39]5)[C:25]=4[N:26]=3)=[CH:18][CH:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:43](OCCCC)=[CH2:44].C(N(C(C)C)CC)(C)C>ClCCl.[Pd](Cl)Cl.C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[CH-]1C=CC=C1.[Fe+2].C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[CH-]1C=CC=C1.[Fe+2].C(O)CCC>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([C:14]2[CH:15]=[N:16][C:17]([NH:20][C:21]3[N:22]=[CH:23][C:24]4[C:30]([CH3:31])=[C:29]([C:32]([O:34][CH2:35][CH2:36][CH2:43][CH3:44])=[CH2:33])[C:28](=[O:37])[N:27]([CH:38]5[CH2:39][CH2:40][CH2:41][CH2:42]5)[C:25]=4[N:26]=3)=[CH:18][CH:19]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 8108Butyl vinyl etherHCID 81531DiisopropylethylamineHCID 112731704-{6-[8-Cyclopentyl-6-(1-ethoxy-vinyl)-5-methyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino]-pyridin-3-yl}-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 44248250tert-Butyl 4-(6-((6-(1-Butoxyethenyl)-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido(2,3-d)pyrimidin-2-yl)amino)-pyridin-3-yl)-piperazine-1-carboxylateYield 75.2%

Reagents, catalysts & solvents 2

HCID 178478481HCID 178478481, compoundCatalystHCID 2631-ButanolSolvent

Conditions

Temperature
95 °C

Procedure

A 5-L, three-necked, round-bottomed flask, equipped with a mechanical stirrer, a thermocouple, and a nitrogen inlet/outlet vented through a silicone oil bubbler was placed under a nitrogen atmosphere and charged with 4-[6-(6-bromo-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino)-pyridin-3-yl]-piperazine-1-carboxylic acid tert-butyl ester (300 g, 0.51 mol, prepared as in Example 2), butyl vinyl ether (154 g, 1.54 mol, ALDRICH), n-butanol (1.5 L, ALDRICH), and diisopropyl ethylamine (107 mL, 0.62 mol, ALDRICH). The slurry was placed under approximately 50 Torr vacuum and then refilled with nitrogen 3 times. To this was added 8.3 g (0.01 mol) bis-(diphenylphosphinoferrocene) palladium dichloride dichloromethane (JOHNSON MATTHEY, Lot 077598001) and the resulting slurry was purged an additional three times as described above. The mixture was then heated to 95° C. and stirred for 20 h. The resulting thin red slurry was diluted with 2 L of heptane and cooled to approximately 5° C. At this temperature, 400 mL saturated aqueous potassium carbonate was added and the mixture was filtered and rinsed with 250 mL of heptane. After drying in an oven for 16 h at 45° C., 231.7 g (75% yield) of the title compound was obtained as a yellow solid.

Workup

  1. additionrefilled with nitrogen 3 times
  2. customthe resulting slurry was purged an additional three times
  3. additionThe resulting thin red slurry was diluted with 2 L of heptane
  4. temperaturecooled to approximately 5° C
  5. additionAt this temperature, 400 mL saturated aqueous potassium carbonate was added
  6. filtrationthe mixture was filtered
  7. washrinsed with 250 mL of heptane
  8. customAfter drying in an oven for 16 h at 45° C.

Sources & evidence

ORD record
ord-e94c55e8ea7c4c24b3abba5c4ff6db02
Source dataset
uspto-grants-2011_01
Patent number
US07863278B2

Reaction notes

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