Ammonium Chloride → HCID 118036402, compound

HRID 1778045Notes

Reaction equation

HRID 1778045 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:11][O:12][CH:13]([O:39][CH3:40])[C:14]1[N:23]=[C:22]2[C:17]([CH2:18][CH2:19][CH2:20][N:21]2[C:24](OC2C=CC=CC=2)=[O:25])=[CH:16][C:15]=1[CH:33]1[CH2:38][CH2:37][O:36][CH2:35][CH2:34]1.[NH2:41][C:42]1[CH:49]=[C:48]([NH:50][CH2:51][CH2:52][O:53][CH3:54])[C:45]([C:46]#[N:47])=[CH:44][N:43]=1.[NH4+].[Cl-]>C1COCC1>[C:46]([C:45]1[C:48]([NH:50][CH2:51][CH2:52][O:53][CH3:54])=[CH:49][C:42]([NH:41][C:24]([N:21]2[C:22]3[C:17](=[CH:16][C:15]([CH:33]4[CH2:34][CH2:35][O:36][CH2:37][CH2:38]4)=[C:14]([CH:13]([O:39][CH3:40])[O:12][CH3:11])[N:23]=3)[CH2:18][CH2:19][CH2:20]2)=[O:25])=[N:43][CH:44]=1)#[N:47]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 118036760HCID 118036760, compound2×HCID 1180369516-Amino-4-(2-methoxyethylamino)pyridine-3-carbonitrile2×

Product 1

HCID 118036402HCID 118036402, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of LHMDS in THF (0.9 M, 2.32 ml, 2.09 mmol) was added to phenyl 7-(dimethoxymethyl)-6-(tetrahydro-2H-pyran-4-yl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate (intermediate 311, 700 mg, 0.95 mmol) and 6-amino-4-((2-methoxyethyl)amino)nicotinonitrile (intermediate 75, 183 mg, 0.95 mmol) in THF (10 ml) cooled at −78° C. with a dry ice/acetone bath. After stirring for 2 h at −78° C. aqueous NH4Cl was added, the mixture warmed to room temperature and extracted with EtOAc. The organic layer was washed with brine, dried over MgSO4 and evaporated. The residue was then purified by normal phase chromatography using a 24 g RediSep® column, eluting with a gradient from hexane to 50% EtOAc in hexane. Product containing fractions were then combined and evaporated to give the title compound as a white solid. (UPLC-MS 3) tR 1.07 min; ESI-MS 511.4 [M+H]+.

Workup

  1. additionwas added
  2. temperaturethe mixture warmed to room temperature
  3. extractionextracted with EtOAc
  4. washThe organic layer was washed with brine
  5. dry with materialdried over MgSO4
  6. customevaporated
  7. customThe residue was then purified by normal phase chromatography
  8. washeluting with a gradient from hexane to 50% EtOAc in hexane
  9. additionProduct containing fractions
  10. customevaporated

Sources & evidence

ORD record
ord-298510eefbd44e82a44289ae7f2fa924
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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