2-Methyltetrahydrofuran → HCID 178480322, compound

HRID 874076Notes

Reaction equation

HRID 874076 reaction equation
[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][C@H:3]1[C:7]1[CH:8]=[C:9]([O:13][CH2:14][CH2:15][NH2:16])[CH:10]=[N:11][CH:12]=1.[C:17]([O:21][C:22]([C@H]1CC[C@H](C(O)=O)CC1)=[O:23])([CH3:20])([CH3:19])[CH3:18].C(P1(=O)OP(CCC)(=O)OP(C[CH2:48][CH3:49])(=O)O1)CC.CC[N:53](CC)CC.[CH3:58][CH:59]1[CH2:63][CH2:62][CH2:61][O:60]1>>[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][C@H:3]1[C:7]1[CH:8]=[C:9]([O:13][CH2:14][CH2:15][NH:16][C:61]([C@H:62]2[CH2:49][CH2:48][C@H:58]([NH:53][C:22](=[O:23])[O:21][C:17]([CH3:18])([CH3:19])[CH3:20])[CH2:59][CH2:63]2)=[O:60])[CH:10]=[N:11][CH:12]=1

Participants

6

Reactant 5

HCID 73012-MethyltetrahydrofuranHCID 8471TriethylamineHCID 111923Propylphosphonic anhydride2×HCID 54675478(S)-2-(5-(1-methylpyrrolidin-2-yl)pyridin-3-yloxy)ethanamineHCID 178451160HCID 178451160, compound

Product 1

HCID 178480322HCID 178480322, compoundYield 35%

Procedure

A solution of 2-({5-[(2S)-1-methylpyrrolidin-2-yl]pyridin-3-yl}oxy)ethanamine (preparation 12) (55 mg, 0.25 mmol) in 2-methyltetrahydrofuran (2 ml) was treated, with stirring, with trans-4-tert-butoxycarbonyl-cyclohexane carboxylic acid (91 mg, 0.373 mmol) followed by T3P (317 μl, 0.498 mmol) and the Et3N(118 μl, 0.91 mmol). After stirring for 3 hours, the solution was treated with T3P (69 μL, 0.498 mmole). After stirring for 18 hours the solution was concentrated in vacuo and the residue was taken up in MeOH and applied to an SCX-2 cartridge which was eluted with methanol followed by ammonia in MeOH (˜2M). Product containing fractions were concentrated in vacuo and the residue purified by column chromatography on silica gel eluting with EtOAc:MeOH:NH3 (gradient from 1:0:0 to 90:10:1). This material was then dissolved in DCM and treated with PS-Isocyanate resin for 3 hours then filtered and evaporated in-vacuo to give the title compound as a pale yellow gum (35 mg, 35%);

Workup

  1. stirringAfter stirring for 18 hours the solution
  2. concentrationwas concentrated in vacuo
  3. washwas eluted with methanol
  4. additionProduct containing fractions
  5. concentrationwere concentrated in vacuo
  6. customthe residue purified by column chromatography on silica gel eluting with EtOAc
  7. dissolutionThis material was then dissolved in DCM
  8. additiontreated with PS-Isocyanate resin for 3 hours
  9. filtrationthen filtered
  10. customevaporated in-vacuo

Sources & evidence

ORD record
ord-05e2c4e52103451a93a8a4c08ef17ead
Source dataset
uspto-grants-2015_03
Patent number
US08980276B2

Reaction notes

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