HCID 53246866, compound → HCID 53247606, compound

HRID 527500Notes

Reaction equation

HRID 527500 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9](=[O:43])[N:10]([C@H:13]2[C@H:17]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([F:25])[CH:19]=3)[CH2:16][N:15]([C:26]([CH:28]3[CH2:33][CH2:32][N:31]([C:34]4[CH:39]=[CH:38][C:37]([C:40](=[O:42])[CH3:41])=[CH:36][N:35]=4)[CH2:30][CH2:29]3)=[O:27])[CH2:14]2)[CH2:11][CH3:12])=[CH:4][CH:3]=1.[CH3:44][Mg]I>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9](=[O:43])[N:10]([C@H:13]2[C@H:17]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([F:25])[CH:19]=3)[CH2:16][N:15]([C:26]([CH:28]3[CH2:29][CH2:30][N:31]([C:34]4[CH:39]=[CH:38][C:37]([C:40]([OH:42])([CH3:44])[CH3:41])=[CH:36][N:35]=4)[CH2:32][CH2:33]3)=[O:27])[CH2:14]2)[CH2:11][CH3:12])=[CH:4][CH:3]=1

Participants

3

Reactant 2

HCID 53246866HCID 53246866, compoundHCID 178418373HCID 178418373, compound

Product 1

HCID 53247606HCID 53247606, compoundYield 13.2%

Procedure

A mixture of 142 mg (0.23 mmol) [(3S,4R)-1-(5′-Acetyl-3,4,5,6-tetrahydro-2H-[1,2]bipyridinyl-4-carbonyl)-4-(4-chloro-3-fluoro-phenyl)-pyrrolidin-3-yl]-ethyl-carbamic acid 4-fluoro-phenyl ester (example 59) and 0.097 mL (0.29 mmol) methylmagnesium iodide (3M) in 5 mL was stirred from 0° to 15° C. during 90 min and quenched at 0° C. with NH4Cl (aq.). The mixture was extracted with ethyl acetate and the combined organic layers were dried with Na2SO4 and evaporated. The residue was subjected to preparative HPLC on reversed phase eluting with a gradient formed from acetonitrile, water and NEt3. The product containing fractions were evaporated to yield 19 mg (13%) of the title compound as white solid. MS m/e: 627.2 [M+11]+.

Workup

  1. customquenched at 0° C. with NH4Cl (aq.)
  2. extractionThe mixture was extracted with ethyl acetate
  3. dry with materialthe combined organic layers were dried with Na2SO4
  4. customevaporated
  5. washeluting with a gradient
  6. customformed from acetonitrile, water and NEt3
  7. additionThe product containing fractions
  8. customwere evaporated

Sources & evidence

ORD record
ord-1e00184b6ba8485b810934cda28c1d5a
Source dataset
uspto-grants-2016_05
Patent number
US09346786B2

Reaction notes

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