Ammonium Chloride → N-(5-cyano-4-(2-methoxyethoxy)pyridin-2-yl)-6-cyclopropyl-7-formyl-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

HRID 1778087ノート

反応式

HRID 1778087 の反応式
C1(C2C=C3C(=NC=2C(OC)OC)N(C(OC2C=CC=CC=2)=O)CCC3)CC1.NC1C=C(OCCOC)C(C#N)=CN=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[NH4+].[Cl-].[C:54]([C:56]1[C:57]([O:83][CH2:84][CH2:85][O:86][CH3:87])=[CH:58][C:59]([NH:62][C:63]([N:65]2[C:74]3[C:69](=[CH:70][C:71]([CH:80]4[CH2:82][CH2:81]4)=[C:72]([CH:75](OC)[O:76]C)[N:73]=3)[CH2:68][CH2:67][CH2:66]2)=[O:64])=[N:60][CH:61]=1)#[N:55]>C1COCC1>[C:54]([C:56]1[C:57]([O:83][CH2:84][CH2:85][O:86][CH3:87])=[CH:58][C:59]([NH:62][C:63]([N:65]2[C:74]3[C:69](=[CH:70][C:71]([CH:80]4[CH2:82][CH2:81]4)=[C:72]([CH:75]=[O:76])[N:73]=3)[CH2:68][CH2:67][CH2:66]2)=[O:64])=[N:60][CH:61]=1)#[N:55]

参加物

7

反応物 5

HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 118036355N-(5-cyano-4-(2-methoxyethoxy)pyridin-2-yl)-6-cyclopropyl-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamideHCID 118036693phenyl 6-cyclopropyl-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate2 回HCID 1180368416-Amino-4-(2-methoxyethoxy)nicotinonitrile2 回

生成物 1

HCID 118036418N-(5-cyano-4-(2-methoxyethoxy)pyridin-2-yl)-6-cyclopropyl-7-formyl-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-78 °C

実験手順

To a solution of phenyl 6-cyclopropyl-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate (intermediate 51A, 52 mg, 0.141 mmol) and 6-amino-4-(2-methoxyethoxy)nicotinonitrile (intermediate 20, 30.0 mg, 0.155 mmol) in THF (1 ml) at −78° C. was slowly added LHMDS (1 M in THF, 0.311 ml, 0.311 mmol). The reaction mixture was stirred at −78° C. for 30 min and then allowed to warm to room temperature. The reaction mixture was poured into sat. aq. NH4Cl and extracted twice with DCM. The organic phase was then dried over Na2SO4, filtered and concentrated. The residue was subjected to reverse phase chromatography (13 g C18 cartridge, 0.1% TFA in water/acetonitrile 90:10 to 0:100) to give a mixture of title compound and N-(5-cyano-4-(2-methoxyethoxyl)pyridin-2-yl)-6-cyclopropyl-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide as an off-white powder. This material was dissolved in THF (2 ml) and H2O (2 ml), treated with conc. HCl (1.0 ml), the reaction mixture was stirred at room temperature for 1 h. The reaction mixture was poured into sat. aq. NaHCO3 and extracted with DCM (2×). The organic phase was then dried over Na2SO4, filtered and concentrated to give the title compound as a light brown powder.

後処理

  1. customat −78° C.
  2. temperatureto warm to room temperature
  3. extractionextracted twice with DCM
  4. dry with materialThe organic phase was then dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give

出典と根拠

ORDレコード
ord-37d7f023b0ed4eee994dd23ae36214d3
出典データセット
uspto-grants-2016_02
特許番号
US09266883B2

反応ノート

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