Pyridine, hydrofluoride (1:1) → N-(5-cyano-4-isopropoxypyridin-2-yl)-7-(dimethoxymethyl)-6-(hydroxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

HRID 1777985Notes

Reaction equation

HRID 1777985 reaction equation
C1C=CN=CC=1.F.[Si]([O:15][CH2:16][C:17]1[CH:18]=[C:19]2[C:24](=[N:25][C:26]=1[CH:27]([O:30][CH3:31])[O:28][CH3:29])[N:23]([C:32]([NH:34][C:35]1[CH:40]=[C:39]([O:41][CH:42]([CH3:44])[CH3:43])[C:38]([C:45]#[N:46])=[CH:37][N:36]=1)=[O:33])[CH2:22][CH2:21][CH2:20]2)(C(C)(C)C)(C)C>C1COCC1>[C:45]([C:38]1[C:39]([O:41][CH:42]([CH3:44])[CH3:43])=[CH:40][C:35]([NH:34][C:32]([N:23]2[C:24]3[C:19](=[CH:18][C:17]([CH2:16][OH:15])=[C:26]([CH:27]([O:30][CH3:31])[O:28][CH3:29])[N:25]=3)[CH2:20][CH2:21][CH2:22]2)=[O:33])=[N:36][CH:37]=1)#[N:46]

Participants

4

Reactant 2

HCID 64774Pyridine, hydrofluoride (1:1)HCID 1317347956-(((tert-butyldimethylsilyl)oxy)methyl)-N-(5-cyano-4-isopropoxypyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide2×

Product 1

HCID 118036998N-(5-cyano-4-isopropoxypyridin-2-yl)-7-(dimethoxymethyl)-6-(hydroxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

HF-Pyridine (300 μL, 3.33 mmol) was added to a solution of 6-(((tert-butyldimethylsilyl)oxy)methyl)-N-(5-cyano-4-isopropoxypyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide (intermediate 165, 861 mg, 1.549 mmol) in THF (8 ml) at room temperature. The reaction mixture was stirred for 5 h and 20 min, quenched with saturated aqueous NaHCO3 and partitioned with ethyl acetate. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with brine, dried using Na2SO4, filtered and concentrated to yield the title compound as a white solid. (UPLC-MS 3) tR 1.11 min; ESI-MS 442.1 [M+H]+; 1H NMR (400 MHz, CDCl3) δ 13.92 (s, 1H), 8.36 (s, 1H), 7.95 (s, 1H), 7.55 (s, 1H), 5.46 (s, 1H), 4.90-4.79 (m, 1H), 4.72 (d, 2H), 4.08-4.00 (m, 2H), 3.54 (s, 6H), 2.86 (t, 2H), 2.07-1.95 (m, 2H), 1.57 (br s, 1H), 1.44 (d, 6H).

Workup

  1. customquenched with saturated aqueous NaHCO3
  2. custompartitioned with ethyl acetate
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. washthe combined organic layers were washed with brine
  5. customdried
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-8a473a771d5a484f895603dd7b2fb901
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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