Isopropanol → 6-Amino-4-isopropoxynicotinonitrile

HRID 1777955Notes

Reaction equation

HRID 1777955 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH3:11][CH:12]([OH:14])[CH3:13].[NH2:15][C:16]1[CH:23]=[C:22](F)[C:19]([C:20]#[N:21])=[CH:18][N:17]=1>C1COCC1>[NH2:15][C:16]1[CH:23]=[C:22]([O:14][CH:12]([CH3:13])[CH3:11])[C:19]([C:20]#[N:21])=[CH:18][N:17]=1

Participants

5

Reactant 3

HCID 3776IsopropanolHCID 3251421Potassium bis(trimethylsilyl)amideHCID 1180369016-Amino-4-fluoronicotinonitrile2×

Product 1

HCID 1180369706-Amino-4-isopropoxynicotinonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of KHMDS (87 g, 438 mmol) was added portionwise to a solution of propan-2-ol (26.3 g, 438 mmol) in THF (250 ml) at room temperature. After 15 min a solution of 6-amino-4-fluoronicotinonitrile (intermediate 21, 30 g, 219 mmol) in THF (200 ml) was added and the reaction mixture stirred for 18 h at room temperature. The reaction mixture was partitioned between saturated aqueous NH4Cl and EtOAc, extracted with EtOAc (2×), the combined EtOAc layers were dried over Na2SO4 and evaporated. The residue was triturated with Et2O and the product obtained by filtration as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 8.12 (s, 1H), 6.82 (s, 2H), 6.07 (s, 1H), 4.64 (septet, 1H), 1.31 (d, 6H). (UPLC-MS 7) tR 0.61; ESI-MS 178.1 [M+H]+.

Workup

  1. customThe reaction mixture was partitioned between saturated aqueous NH4Cl and EtOAc
  2. extractionextracted with EtOAc (2×)
  3. dry with materialthe combined EtOAc layers were dried over Na2SO4
  4. customevaporated
  5. customThe residue was triturated with Et2O
  6. customthe product obtained by filtration as a yellow solid

Sources & evidence

ORD record
ord-2f657d81e665480a8c4a5f08a6bbdb5d
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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