(6-Methoxy-benzo[b]thiophen-2-yl)-methanol → tert-Butyl (tert-butoxycarbonyl {6-[(6-methoxybenzo[b]thiophen-2-ylmethyl)(pyridin-3-ylsulfonyl)aminomethyl]pyridin-2-yl}amino)acetate

HRID 241258Notes

Reaction equation

HRID 241258 reaction equation
[C:1]([O:5][C:6](=[O:33])[CH2:7][N:8]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][NH:16][S:17]([C:20]2[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=2)(=[O:19])=[O:18])[N:10]=1)([CH3:4])([CH3:3])[CH3:2].S1C=CN=C1C1C=CC(CNS(C2C=NC=CC=2)(=O)=O)=CC=1.[CH3:56][O:57][C:58]1[CH:59]=[CH:60][C:61]2[CH:65]=[C:64]([CH2:66]O)[S:63][C:62]=2[CH:68]=1>>[C:1]([O:5][C:6](=[O:33])[CH2:7][N:8]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH:15]([CH2:66][C:64]2[S:63][C:62]3[CH:68]=[C:58]([O:57][CH3:56])[CH:59]=[CH:60][C:61]=3[CH:65]=2)[NH:16][S:17]([C:20]2[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=2)(=[O:18])=[O:19])[N:10]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 3

HCID 57608293(6-Methoxy-benzo[b]thiophen-2-yl)-methanolHCID 66717376N-[4-(thiazol-2-yl)benzyl]pyridin-3-ylsulfonamideHCID 86651773Tert-butyl (tert-butoxycarbonyl{6-[(pyridin-3-ylsulfonyl)aminomethyl]pyridin-2-yl}amino)acetate

Product 1

HCID 86651777tert-Butyl (tert-butoxycarbonyl {6-[(6-methoxybenzo[b]thiophen-2-ylmethyl)(pyridin-3-ylsulfonyl)aminomethyl]pyridin-2-yl}amino)acetateYield 78%

Procedure

Reaction was carried out in the same manner as in Example 2-(a) except for using tert-butyl(tert-butoxycarbonyl{6-[(pyridin-3-ylsulfonyl)aminomethyl]pyridin-2-yl}amino)acetate (69.4 mg, 0.145 mmol) obtained in Reference Example 12-(d) in place of N-[4-(thiazol-2-yl)benzyl]pyridin-3-ylsulfonamide, and using (6-methoxybenzo[b]-thiophen-2-yl)methanol (see WO 2006/106711A, 33.9 mg, 0.175 mmol) in place of tert-butyl [tert-butoxycarbonyl(6-hydroxymethylpyridin-2-yl)amino]acetate. After completion of the reaction, the reaction solution was concentrated under reduced pressure, and water was added to the residue, followed by extraction with toluene. The separated organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography (eluent; hexane:ethyl acetate=3:1→1:1 (V/V)) and then to reversed phase column chromatography (column; Megabond Elut™ C18 (manufactured by Varian, Inc.), eluent; acetonitrile:water=1:1→1:0 (V/V)), and fractions containing the desired compound were concentrated under reduced pressure to afford the title compound (73.8 mg) as a white foam. (Yield: 78%)

Workup

  1. customReaction
  2. customAfter completion of the reaction
  3. concentrationthe reaction solution was concentrated under reduced pressure, and water
  4. additionwas added to the residue
  5. extractionfollowed by extraction with toluene
  6. dry with materialThe separated organic layer was dried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. additionto reversed phase column chromatography (column; Megabond Elut™ C18 (manufactured by Varian, Inc.), eluent; acetonitrile:water=1:1→1:0 (V/V)), and fractions containing the desired compound
  9. concentrationwere concentrated under reduced pressure

Sources & evidence

ORD record
ord-3bafa36f8e0d495d82d467c77511f4e2
Source dataset
uspto-grants-2014_02
Patent number
US08648097B2

Reaction notes

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