Hydrochloric Acid → 1-[(Cyclopropylmethyl)amino]-4-hydroxy-3-{7-[(methoxymethoxy)methyl]-1,1-dioxido-4h-thieno[2,3-e][1,2,4]thiadiazin-3-yl}quinolin-2(1h)-one

HRID 601333Notes

Reaction equation

HRID 601333 reaction equation
[CH:1]1([CH:4]=[N: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[S:23][CH:24]=[C:25]([CH2:26][O:27][CH2:28][O:29][CH3:30])[C:20]=4[S:19](=[O:32])(=[O:31])[N:18]=3)[C:7]2=[O:33])[CH2:3][CH2:2]1.CO.[BH4-].[Li+].Cl>O1CCCC1.O>[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[S:23][CH:24]=[C:25]([CH2:26][O:27][CH2:28][O:29][CH3:30])[C:20]=4[S:19](=[O:31])(=[O:32])[N:18]=3)[C:7]2=[O:33])[CH2:2][CH2:3]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 4148881Lithium borohydrideHCID 1363584131-{[cyclopropylmethylene]amino}-4-hydroxy-3-{7-[(methoxymethoxy)methyl]-1,1-dioxido-4H-thieno[2,3-e][1,2,4]thiadiazin-3-yl}quinolin-2(1H)-one

Product 1

HCID 1359745791-[(Cyclopropylmethyl)amino]-4-hydroxy-3-{7-[(methoxymethoxy)methyl]-1,1-dioxido-4h-thieno[2,3-e][1,2,4]thiadiazin-3-yl}quinolin-2(1h)-oneYield 53%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
25 °C

Procedure

The product of Example 350F (78.9 mg, 0.16 mmol) in tetrahydrofuran (4 mL) and methanol (0.013 mL, 0.32 mmol) at 0° C. was treated dropwise with a 2.0 M solution of lithium borohydride in tetrahydrofuran (0.131 mL, 0.24 mmol). The reaction was stirred at 25° C. for 1 hour, acidified with 1N hydrochloric acid to approximately pH 2-4, diluted with water (20 mL), and the resulting precipitate was collected by filtration and dried. The crude product was chromatographed on silica gel with 2% methanol/dichloromethane to give the title compound (41.6 mg, 52.5%). The sodium salt of the title compound was prepared according to the procedure of Example 1D. 1H NMR (300 MHz, DMSO-d6) δ 0.15 (d, J=4.41 Hz, 2 H), 0.42 (d, J=8.09 Hz, 2 H), 1.01 (m, 1 H), 2.84 (d, J=6.62 Hz, 2 H), 4.64 (s, 2 H), 4.71 (s, 2 H), 6.36 (br.s, 1 H), 7.41 (m, 2 H), 7.88 (t, J=7.35 Hz, 1 H), 8.07 (d, J=8.46 Hz, 1 H), 8.16 (d, J=8.09 Hz, 1 H). MS (ESI−) m/z 489 (M−H)−.

Workup

  1. filtrationthe resulting precipitate was collected by filtration
  2. customdried
  3. customThe crude product was chromatographed on silica gel with 2% methanol/dichloromethane

Sources & evidence

ORD record
ord-e60b091538694c988a79757f697d59cc
Source dataset
uspto-grants-2011_03
Patent number
US07902203B2

Reaction notes

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