Thionyl Chloride → HCID 178517357, compound

HRID 892125Notes

Reaction equation

HRID 892125 reaction equation
[CH2:1]([N:8]1[C:16]2[C:11](=[N:12][C:13](Cl)=[N:14][C:15]=2[NH:17][C@H:18]([CH2:21][C:22]2[CH:27]=[CH:26][C:25](F)=[CH:24][CH:23]=2)[CH2:19]O)[N:10]=[C:9]1[CH:30]1[CH2:34][CH2:33][CH2:32][CH2:31]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)(Cl)=[O:36]>>[CH2:1]([N:8]1[C:16]2[C:15]3=[N:17][C@H:18]([CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[CH2:19][N:14]3[C:13](=[O:36])[NH:12][C:11]=2[N:10]=[C:9]1[CH:30]1[CH2:34][CH2:33][CH2:32][CH2:31]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

3

Reactant 2

HCID 24386Thionyl ChlorideHCID 86589633HCID 86589633, compound

Product 1

HCID 178517357HCID 178517357, compound

Procedure

To Compound C3 obtained in Reference Example 38 was added thionyl chloride, and a cyclized compound was obtained in a manner similar to that in Example 66. From the resulting cyclized compound, a hydrolyzed compound was obtained in a manner similar to the method by which Compound 77a was obtained from the Compound 66 in Example 77. From the resulting hydrolyzed compound (590 mg, 1.33 mmol) and 2-(2-bromoethoxy)tetrahydro-2H-pyran (400 μL, 2.65 mmol, 2.0 equivalents), an adduct (0.56 g, 74%) was obtained in a manner similar to that in Example 79, and the residue was dissolved in methanol (10 mL). To the mixture was added p-toluenesulfonic acid monohydrate and the mixture was stirred with heating at 60° C. for 2 hours. The reaction solution was concentrated and directly purified by silica gel column chromatography (chloroform:methanol=98:2 to 97:3). Then, the title compound in the free form was obtained in a manner similar to the method by which Compound 40 was obtained from Adduct 40a in Example 40. To the resulting free compound were added a 4 mol/L solution of hydrogen chloride in dioxane (2 mL) and methanol (2 mL), the mixture was concentrated, and the residue was crystallized from acetone and diethyl ether to obtain the title compound (210 mg, 49%) as a white solid.

Workup

  1. customa cyclized compound was obtained in a manner similar to that in Example 66

Sources & evidence

ORD record
ord-972443d5da314d369f10b72640273cb1
Source dataset
uspto-grants-2006_02
Patent number
US07005430B2

Reaction notes

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