Methanol → HCID 10319559, compound

HRID 1611530Notes

Reaction equation

HRID 1611530 reaction equation
C[O:2][C:3](=O)[CH2:4][CH2:5][CH2:6][C:7]1[S:30][C:10]2=[N:11][CH:12]=[C:13]([C:28]#[N:29])[C:14]([NH:15][C:16]3[CH:21]=[C:20]([O:22][CH3:23])[C:19]([O:24][CH3:25])=[C:18]([O:26][CH3:27])[CH:17]=3)=[C:9]2[CH:8]=1.[BH4-].[Li+].CO>O1CCCC1>[OH:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]1[S:30][C:10]2=[N:11][CH:12]=[C:13]([C:28]#[N:29])[C:14]([NH:15][C:16]3[CH:17]=[C:18]([O:26][CH3:27])[C:19]([O:24][CH3:25])=[C:20]([O:22][CH3:23])[CH:21]=3)=[C:9]2[CH:8]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 4148881Lithium borohydrideHCID 10003428HCID 10003428, compound

Product 1

HCID 10319559HCID 10319559, compoundYield 54.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-[5-cyano-4-(3,4,5-trimethoxyphenylamino)-thieno[2,3-b]pyridin-2-yl]-butyric acid methyl ester (1.10 g, 2.5 mmol) in 15 mL of tetrahydrofuran at room temperature is added dropwise lithium borohydride in tetrahydrofuran (10 mL, 2.0 M, 20 mmol). The mixture is heated at reflux for 1 hour, and cooled to room temperature. Methanol (20 mL) is added, and stirring is continued at room temperature overnight. The reaction mixture is partitioned between saturated aqueous sodium chloride and ethyl acetate. The organic layer is dried, and concentrated. The residue is purified by flash column chromatography eluting with 2:1 ethyl acetate:hexane to provide 563 mg of 2-(4-hydroxybutyl)-4-[(3,4,5-trimethoxyphenyl)amino]-thieno[2,3-b]pyridine-5-carbonitrile as a white solid, mp 125-127° C.; 1H NMR (DMSO-d6) δ 1.50 (m, 2H), 1.72 (m, 2H), 2.91 (t, J=7 Hz, 2H), 3.42 (m, 2H), 3.68 (s, 3H), 3.76 (s, 6H), 4.42 (t, J=5 Hz, 1H), 6.75 (s, 2H), 7.44 (s, 1H), 8.45 (s, 1H), 10.23 (s, 1H); MS 414.4 (M+H)+.

Workup

  1. temperatureThe mixture is heated
  2. temperatureat reflux for 1 hour
  3. customThe reaction mixture is partitioned between saturated aqueous sodium chloride and ethyl acetate
  4. customThe organic layer is dried
  5. concentrationconcentrated
  6. customThe residue is purified by flash column chromatography
  7. washeluting with 2:1 ethyl acetate

Sources & evidence

ORD record
ord-7e31b8d39fe34d5195244e299413cb8a
Source dataset
uspto-grants-2006_01
Patent number
US06987116B2

Reaction notes

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