1,1'-Carbonyl-di-(1,2,4-triazole) → 6-(2-oxa-5-azaspiro[3.4]octan-5-ylmethyl)-N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

HRID 1777971Notes

Reaction equation

HRID 1777971 reaction equation
N1([C:6](N2C=NC=N2)=[O:7])C=NC=N1.[NH2:13][C:14]1[CH:21]=[C:20]([NH:22][CH2:23][CH2:24][O:25][CH3:26])[C:17]([C:18]#[N:19])=[CH:16][N:15]=1.[CH3:27][O:28][CH:29]([O:49][CH3:50])[C:30]1[C:39]([CH2:40][N:41]2[CH2:48][CH2:47][CH2:46][C:42]32[CH2:45][O:44][CH2:43]3)=[CH:38][C:37]2[CH2:36][CH2:35][CH2:34][NH:33][C:32]=2[N:31]=1>CN(C=O)C>[CH2:43]1[C:42]2([CH2:46][CH2:47][CH2:48][N:41]2[CH2:40][C:39]2[CH:38]=[C:37]3[C:32](=[N:31][C:30]=2[CH:29]([O:28][CH3:27])[O:49][CH3:50])[N:33]([C:6]([NH:13][C:14]2[CH:21]=[C:20]([NH:22][CH2:23][CH2:24][O:25][CH3:26])[C:17]([C:18]#[N:19])=[CH:16][N:15]=2)=[O:7])[CH2:34][CH2:35][CH2:36]3)[CH2:45][O:44]1

Participants

5

Reactant 3

HCID 43939611,1'-Carbonyl-di-(1,2,4-triazole)HCID 1180367515-((2-(Dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-2-oxa-5-azaspiro[3.4]octane2×HCID 1180369516-Amino-4-(2-methoxyethylamino)pyridine-3-carbonitrile2×

Product 1

HCID 1180366486-(2-oxa-5-azaspiro[3.4]octan-5-ylmethyl)-N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

A solution of di(1H-1,2,4-triazol-1-yl)methanone (320 mg, 1.95 mmol) in DMF (7 ml) was added to a mixture of 6-amino-4-((2-methoxyethyl)amino)nicotinonitrile (intermediate 75, 375 mg, 1.95 mmol) in anhydrous DMF (1.5 ml) at 0° C. After stirring for 2.5 h at room temperature a solution of 5-((2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-2-oxa-5-azaspiro[3.4]octane (intermediate 230C, 260 mg, 0.78 mmol) in DMF (3 ml) was added. The reaction mixture was stirred for 17.5 h at room temperature, then partitioned between saturated aqueous NaHCO3 solution and EtOAc, the EtOAc phase washed with brine, dried over MgSO4 and evaporated. The residue was applied to a silica column and purified by normal phase chromatography, eluting with EtOAc then a gradient from DCM to 10% MeOH in DCM. Product containing fractions were combined and evaporated to give the title compound as a pale yellow solid. (UPLC-MS 3) Rt=0.92 min; MS m/z [M+H]+ 552.

Workup

  1. additionwas added
  2. custompartitioned between saturated aqueous NaHCO3 solution and EtOAc
  3. washthe EtOAc phase washed with brine
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. custompurified by normal phase chromatography
  7. washeluting with EtOAc
  8. additionProduct containing fractions
  9. customevaporated

Sources & evidence

ORD record
ord-80511d67107f48ddb10aec586b95e508
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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