Propyl mercaptan → 3-Ethyl-5-[5-(4-ethylpiperazin-1-ylsulphonyl]-2-methoxypyridin-3-yl]-2-(pyridin-2-yl)methyl-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one

HRID 990229Notes

Reaction equation

HRID 990229 reaction equation
[CH2:1]([O:3][C:4]1[C:9]([C:10]2[NH:11][C:12](=[O:28])[C:13]3[C:14](=[C:16]([CH2:26][CH3:27])[N:17]([CH2:19][C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=4)[N:18]=3)[N:15]=2)=[CH:8][C:7]([S:29]([N:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH3:39])[CH2:34][CH2:33]2)(=[O:31])=[O:30])=[CH:6][N:5]=1)C.C[Si]([N-][Si](C)(C)C)(C)C.[K+].C(S)CC>>[CH2:26]([C:16]1[N:17]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=2)[N:18]=[C:13]2[C:12](=[O:28])[NH:11][C:10]([C:9]3[C:4]([O:3][CH3:1])=[N:5][CH:6]=[C:7]([S:29]([N:32]4[CH2:37][CH2:36][N:35]([CH2:38][CH3:39])[CH2:34][CH2:33]4)(=[O:31])=[O:30])[CH:8]=3)=[N:15][C:14]=12)[CH3:27]

Participants

4

Reactant 3

HCID 7848Propyl mercaptanHCID 3251421Potassium bis(trimethylsilyl)amideHCID 1355816594-{6-Ethoxy-5-[3-ethyl-6,7-dihydro-7-oxo-2-(2-pyridylmethyl)-2H-pyrazolo [4,3-d]pyrimidin-5-yl]-3-pyridylsulfonyl}-1-ethylpiperazine

Product 1

HCID 1358163423-Ethyl-5-[5-(4-ethylpiperazin-1-ylsulphonyl]-2-methoxypyridin-3-yl]-2-(pyridin-2-yl)methyl-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-oneYield 50.1%

Conditions

Temperature
110 °C

Procedure

A stirred mixture of the title compound of Example 1 (350 mg, 0.63 mmol), potassium bis(trimethylsilyl)amide (630 mg, 3.15 mmol) and n-propanethiol (5 ml) was heated in a sealed vessel at 110° C. for 48 hours, then allowed to cool and evaporated under reduced pressure, The residue was azeotroped with dichloromethane:methanol (95:5), then partitioned between water (10 ml) and dichloromethane (15 ml). The phases were separated, the aqueous phase extracted with dichloromethane (2×15 ml) and the combined organic solutions dried (MgSO4) and evaporated under reduced pressure. This residue was purified by column chromatography on silica gel, using dichloromethane:methanol (97:3) as eluant, to yield the title compound (170 mg, 50%) as a yellow is solid. Found: C, 54.50; H, 5.64; N, 19.93. C25H30N8O4S; 0.75H2O requires C, 54.38; H, 5.75; N, 20.29%. δ (CDCl3): 1.02 (3H, t), 1.32 (3H, t,) 2.40 (2H, q), 2.55 (4H, m), 3.06 (2H, q), 3.14 (4H, m), 4.26 (3H, s), 5.68 (2H, s), 7.14 (1H, d), 7.22 (1H, m), 7.64 (1H, m), 8.58 (1H, d), 8.66 (1H, s), 9.05 (1H, s), 10.59 (1H, s). LRMS: m/z 540 (M+2)+.

Workup

  1. temperatureto cool
  2. customevaporated under reduced pressure
  3. customThe residue was azeotroped with dichloromethane:methanol (95:5)
  4. custompartitioned between water (10 ml) and dichloromethane (15 ml)
  5. customThe phases were separated
  6. extractionthe aqueous phase extracted with dichloromethane (2×15 ml)
  7. dry with materialthe combined organic solutions dried (MgSO4)
  8. customevaporated under reduced pressure
  9. customThis residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-87f843e83a144e148a434b70c9270663
Source dataset
uspto-grants-2002_10
Patent number
US06458951B2

Reaction notes

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