(1-Ethoxycyclopropoxy)trimethylsilane → HCID 54689855, compound

HRID 1244117Notes

Reaction equation

HRID 1244117 reaction equation
OC(C(F)(F)F)=O.[Cl:8][C:9]1[S:21][C:12]2[NH:13][C:14](=[O:20])[C:15]([C:18]#[N:19])=[C:16]([OH:17])[C:11]=2[C:10]=1[C:22]1[CH:27]=[CH:26][C:25]([O:28][CH2:29][C:30]2([OH:36])[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)=[CH:24][CH:23]=1.C(O[C:40]1(O[Si](C)(C)C)[CH2:42][CH2:41]1)C.[BH3-]C#N.[Na+]>CO>[Cl:8][C:9]1[S:21][C:12]2[NH:13][C:14](=[O:20])[C:15]([C:18]#[N:19])=[C:16]([OH:17])[C:11]=2[C:10]=1[C:22]1[CH:23]=[CH:24][C:25]([O:28][CH2:29][C:30]2([OH:36])[CH2:35][CH2:34][N:33]([CH:40]3[CH2:42][CH2:41]3)[CH2:32][CH2:31]2)=[CH:26][CH:27]=1

Participants

5

Reactant 3

HCID 2734686(1-Ethoxycyclopropoxy)trimethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 86596544HCID 86596544, compound

Product 1

HCID 54689855HCID 54689855, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 2-chloro-4-hydroxy-3-{4-[(4-hydroxy-piperidin-4-yl)methoxy]phenyl}-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carbonitrile TFA salt (70 mg, 0.128 mmol),[(1-ethoxycyclopropyl)oxy]trimethylsilane (0.103 mL, 0.513 mmol), 3A molecular sieves (30 mg), and NaCNBH3 (32 mg, 0.513 mmol) in MeOH (1 mL) was heated to reflux for 12 h. The reaction was then quenched by the addition of H2O (1 mL) and EtOAc (1 mL). The layers were separated, and the aqueous was extracted with additional EtOAc (2×1 mL). The combined organic layers were dried with anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by RP-HPLC to give the title compound. MS (ESI) m/e 472 (M+H)+; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.84 (m, 2H), 0.94 (m, 2H), 1.80 (d, J=12.0 Hz, 2H), 1.94 (m, 2H), 2.97, (m, 1H), 3.40 (m, 4H), 3.86 (s, 2H), 5.22 (s, 1H), 6.92 (d, J=8.82 Hz, 2H), 7.22 (d, J=8.82 Hz, 2H), 8.81 (s, 1H), 10.77 (s, 1H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 12 h
  3. customThe reaction was then quenched by the addition of H2O (1 mL) and EtOAc (1 mL)
  4. customThe layers were separated
  5. extractionthe aqueous was extracted with additional EtOAc (2×1 mL)
  6. dry with materialThe combined organic layers were dried with anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by RP-HPLC

Sources & evidence

ORD record
ord-b44bee7054c648cdb25a972e63b6ab23
Source dataset
uspto-grants-2006_10
Patent number
US07119205B2

Reaction notes

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