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

HRID 1777990Notes

Reaction equation

HRID 1777990 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]([NH:41][CH2:42][CH2:43][O:44][CH3:45])[C:38]([C:46]#[N:47])=[CH:37][N:36]=1)=[O:33])[CH2:22][CH2:21][CH2:20]2)(C(C)(C)C)(C)C>C1COCC1>[C:46]([C:38]1[C:39]([NH:41][CH2:42][CH2:43][O:44][CH3:45])=[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:47]

Participants

4

Reactant 2

HCID 64774Pyridine, hydrofluoride (1:1)HCID 1317347846-(((tert-butyldimethylsilyl)oxy)methyl)-N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide2×

Product 1

HCID 118036681N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-6-(hydroxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

HF-Pyridine (426 μL, 3.31 mmol) was added to a solution of 6-(((tert-butyldimethylsilyl)oxy)methyl)-N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide (intermediate 74, 900 mg, 1.577 mmol) in THF (7 ml) at room temperature. The reaction mixture was stirred for approximately 2 h, 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 give the title compound as a white solid. (UPLC-MS 3) tR 0.85 min; ESI-MS 457.1 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 13.71 (s, 1H), 8.21 (s, 1H), 7.57 (s, 1H), 7.54 (s, 1H), 5.49 (s, 1H), 5.28 (s, 1H), 4.71 (d, 2H), 4.07-3.99 (m, 2H), 3.67-3.59 (m, 2H), 3.55 (s, 6H), 3.51-3.45 (m, 2H), 3.41 (s, 3H), 2.85 (t, 2H), 2.05-1.96 (m, 2H).

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-5c6b5850238144a68eae1d422de633b5
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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