Lithium borohydride → 3-[7-(2-aminoethoxy)-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl]-1-[(cyclopropylmethyl)amino]-4-hydroxyquinolin-2(1H)-one

HRID 601371Notes

Reaction equation

HRID 601371 reaction equation
[CH:1]1([CH2:4][NH:5][N:6]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]([OH:16])=[C:8]([C:17]3[NH:22][C:21]4[CH:23]=[CH:24][C:25]([O:27][CH2:28][C:29]#[N:30])=[CH:26][C:20]=4[S:19](=[O:32])(=[O:31])[N:18]=3)[C:7]2=[O:33])[CH2:3][CH2:2]1.[Li+].[BH4-]>O1CCCC1.O>[NH2:30][CH2:29][CH2:28][O:27][C:25]1[CH:24]=[CH:23][C:21]2[NH:22][C:17]([C:8]3[C:7](=[O:33])[N:6]([NH:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)[C:15]4[C:10]([C:9]=3[OH:16])=[CH:11][CH:12]=[CH:13][CH:14]=4)=[N:18][S:19](=[O:32])(=[O:31])[C:20]=2[CH:26]=1

Participants

5

Reactant 2

HCID 4148881Lithium borohydrideHCID 136358425[(3-{1-[(cyclopropylmethyl)amino]-4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl}-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl)oxy]acetonitrile

Product 1

HCID 1363584273-[7-(2-aminoethoxy)-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl]-1-[(cyclopropylmethyl)amino]-4-hydroxyquinolin-2(1H)-oneYield 97%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A solution of the product of Example 392A (39 mg, 0.084 mmol) in anhydrous tetrahydrofuran (2 mL) was treated with LiBH4 (1mL, 2M in tetrahydrofuran, 0.2 mmol), stirred at ambient temperature for 30 minutes, then 18 μl water was added and stirred overnight. The solution was diluted with water (20 mL) and extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with brine and dried over anhydrous magnesium sulfate. The slurry was filtered and the solvent removed under reduced pressure to give title compound (38 mg, 97%). 1H NMR (500 MHz, BENZENE-d6) δ 0.20 (d, J=3.05 Hz, 2 H) 0.46 (d, J=7.32 Hz, 2 H) 1.01 (m, 1 H) 2.74 (s, br, 2 H) 2.86 (m, 2 H) 4.19 (t, J=4.90 Hz, 2 H) 5.21 (s, br, 2 H) 6.04 (s, br, 1 H) 7.15 (s, br, 1 H) 7.24 (s, br, 2 H) 7.32 (s, br, 1 H) 7.59 (s, br, 1 H) 7.78 (s, br, 1 H) 8.11 (d, J=7.32 Hz, 1 H) 15.65 (s, br, 1 H). MS (ESI−) m/z 468 (M−H)−.

Workup

  1. stirringstirred overnight
  2. extractionextracted with ethyl acetate (2×50 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationThe slurry was filtered
  6. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-7bfc90f8ea7846bfbc48a7d425687e9d
Source dataset
uspto-grants-2011_03
Patent number
US07902203B2

Reaction notes

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