Potassium tert-butoxide → HCID 51353619, compound

HRID 1879382Notes

Reaction equation

HRID 1879382 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C@@H:9]1[CH2:19][C@@H:18]([OH:20])[C@@H:17]([OH:21])[C:12]2=[N:13][CH:14]=[CH:15][CH:16]=[C:11]2[CH2:10]1.N1([C:27]([N:29]2[CH2:34][CH2:33][CH:32]([N:35]3[C:43]4[C:38](=[N:39][CH:40]=[CH:41][CH:42]=4)[NH:37][C:36]3=[O:44])[CH2:31][CH2:30]2)=[O:28])C=CN=C1.CC(C)([O-])C.[K+]>O1CCCC1>[O:44]=[C:36]1[NH:37][C:38]2=[N:39][CH:40]=[CH:41][CH:42]=[C:43]2[N:35]1[CH:32]1[CH2:31][CH2:30][N:29]([C:27]([O:21][C@H:17]2[C:12]3=[N:13][CH:14]=[CH:15][CH:16]=[C:11]3[CH2:10][C@H:9]([C:3]3[CH:4]=[CH:5][CH:6]=[C:7]([F:8])[C:2]=3[F:1])[CH2:19][C@H:18]2[OH:20])=[O:28])[CH2:34][CH2:33]1

Participants

5

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 58467978HCID 58467978, compoundHCID 584679821-(1-(1H-imidazole-1-carbonyl)piperidin-4-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one2×

Product 1

HCID 51353619HCID 51353619, compoundYield 14.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In an oven-dried 100 mL round-bottom flask was dissolved (6S,8R,9S)-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine-8,9-diol (61 mg, 0.209 mmol) (azeotroped with dry benzene) and 1-(1-(1H-imidazole-1-carbonyl)piperidin-4-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one (65.4 mg, 0.209 mmol) in tetrahydrofuran (2 mL) to give a colorless solution under nitrogen. After cooling to 0° C. (ice bath), potassium t-butoxide (1M in tetrahydrofuran, 0.754 mL, 0.754 mmol) was added dropwise, and the tan suspension was warmed up to room temperature with stirring. After 2 h some SM remained. Another 20 mg of 1-(1-(1H-imidazole-1-carbonyl)piperidin-4-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one was added, and the mixture was left stirring overnight. After 18 h the reaction was quenched with sodium bicarbonate solution and diluted with ethyl acetate. The layers were separated and the aqueous layer was extracted with ethyl acetate twice. The combined organic layers were washed with brine, dried with sodium sulfate, and concentrated to give a yellow oil. Purification by FCC up to 10% methanol/methylene chloride afforded the desired product (last peak, 16 mg, 14%) as a light yellow foam. MS(ESI)[M+H+]=536.26, 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.27-8.59 (m, 1H) 8.08 (dd, J=5.29, 1.26 Hz, 1H) 7.54 (d, J=2.52 Hz, 1H) 7.31-7.51 (m, 1H) 7.22 (dd, J=7.30, 5.04 Hz, 1H) 6.93-7.19 (m, 4H) 5.39-5.63 (m, 1H) 5.18 (br. s., 1H) 4.45-4.64 (m, 1H) 4.37 (br. s., 1H) 3.10-3.40 (m, 3H) 2.92 (d, J=13.85 Hz, 1H) 2.11-2.88 (m, 5H) 1.75-1.95 (m, 2H) 1.55-1.71 (m, 1H).

Workup

  1. customto give a colorless solution under nitrogen
  2. additionwas added dropwise
  3. waitthe mixture was left
  4. stirringstirring overnight
  5. customAfter 18 h the reaction was quenched with sodium bicarbonate solution
  6. additiondiluted with ethyl acetate
  7. customThe layers were separated
  8. extractionthe aqueous layer was extracted with ethyl acetate twice
  9. washThe combined organic layers were washed with brine
  10. dry with materialdried with sodium sulfate
  11. concentrationconcentrated
  12. customto give a yellow oil
  13. customPurification by FCC up to 10% methanol/methylene chloride

Sources & evidence

ORD record
ord-6f50d81a604e48b59afdea5cf1dc8b8f
Source dataset
uspto-grants-2012_11
Patent number
US08314117B2

Reaction notes

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