Acetic Acid → HCID 5330410, compound

HRID 1611515Notes

Reaction equation

HRID 1611515 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[Cl:7][C:8]1[CH:13]=[C:12]([Cl:14])[C:11]([O:15][CH3:16])=[CH:10][C:9]=1[NH:17][C:18]1[C:23]([C:24]#[N:25])=[CH:22][N:21]=[C:20]2[CH:26]=[C:27]([C:29]3[CH:34]=[CH:33][C:32]([CH:35]=O)=[CH:31][CH:30]=3)[S:28][C:19]=12.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>ClCCl.CN(C)C=O>[Cl:7][C:8]1[CH:13]=[C:12]([Cl:14])[C:11]([O:15][CH3:16])=[CH:10][C:9]=1[NH:17][C:18]1[C:23]([C:24]#[N:25])=[CH:22][N:21]=[C:20]2[CH:26]=[C:27]([C:29]3[CH:34]=[CH:33][C:32]([CH2:35][N:1]4[CH2:6][CH2:5][O:4][CH2:3][CH2:2]4)=[CH:31][CH:30]=3)[S:28][C:19]=12

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 8083MorpholineHCID 5049666Sodium triacetoxyborohydrideHCID 10343928HCID 10343928, compound

Product 1

HCID 5330410HCID 5330410, compoundYield 60.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Morpholine (16 mg, 0.18 mmol) is added to a suspension of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-(4-formylphenyl)thieno[3,2-b]pyridine-6-carbonitrile (66 mg, 0.15 mmol) in 5 mL of dichloromethane and 0.5 mL of N,N-dimethylformamide. The reaction mixture is cooled to 0° C. and sodium triacetoxyborohydride (85 mg, 0.40 mmol) is added. After stirring at 0° C. for 1.5 hours, acetic acid (0.02 mL) is added and the reaction mixture is allowed to warm to room temperature and stirred overnight. The reaction is quenched by the addition of water and then partitioned between water and dichloromethane. The organic layer is dried over sodium sulfate, filtered and concentrated in vacuo. The residue is purified by flash column chromatography to provide 48 mg of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-[4-(4-morpholinylmethyl)phenyl]thieno[3,2-b]pyridine-6-carbonitrile as yellow crystals, mp 244-245° C.; 1H NMR (DMSO-d6) δ 2.36 (m, 4H), 3.50 (s, 2H), 3.57 (m, 4H), 3.85 (s, 3H), 7.31 (s, 1H), 7.42 (d, J=8 Hz, 2H), 7.68 (d, J=8 Hz, 2H), 7.76 (s, 1H), 7.89 (s, 1H), 8.60 (s, 1H), 9.73 (s, 1H); MS 525.2 (M+H)+.

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred overnight
  3. customThe reaction is quenched by the addition of water
  4. custompartitioned between water and dichloromethane
  5. dry with materialThe organic layer is dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue is purified by flash column chromatography

Sources & evidence

ORD record
ord-1ef4481e9c8c47b88e5d98cb640ce8ed
Source dataset
uspto-grants-2006_01
Patent number
US06987116B2

Reaction notes

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