2-Methyltetrahydrofuran → HCID 178480320, compound

HRID 874074Notes

Reaction equation

HRID 874074 reaction equation
[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][C@H:3]1[C:7]1[CH:8]=[C:9]([CH2:13][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>>[NH3:2].[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][C@H:3]1[C:7]1[CH:8]=[C:9]([CH2:13][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

7

Reactant 5

HCID 73012-MethyltetrahydrofuranHCID 8471TriethylamineHCID 111923Propylphosphonic anhydride2×HCID 54675475(S)-3-(5-(1-methylpyrrolidin-2-yl)pyridin-3-yl)propan-1-amineHCID 178451160HCID 178451160, compound

Product 2

HCID 222AmmoniaHCID 178480320HCID 178480320, compoundYield 64%

Procedure

A solution of 3-{5-[(2S)-1-methylpyrrolidin-2-yl]pyridin-3-yl}propan-1-amine (preparation 4) (100 mg, 0.45 mmol) in 2-methyltetrahydrofuran (2 ml) was treated, with stirring, with trans-4-tert-butoxycarbonyl-cyclohexane carboxylic acid (132 mg, 0.502 mmol) followed by T3P (580 μl, 0.91 mmol) and then Et3N (118 μl, 0.91 mmol). After stirring for 3 hours, the solution was treated with T3P (240 μL, 0.38 mmol). 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 MeOH 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) to give the title compound as a gum (130 mg, 64%).

Workup

  1. stirringAfter stirring for 18 hours the solution
  2. concentrationwas concentrated in vacuo
  3. washwas eluted with MeOH
  4. additionProduct containing fractions
  5. concentrationwere concentrated in vacuo
  6. customthe residue purified by column chromatography on silica gel eluting with EtOAc

Sources & evidence

ORD record
ord-19d8398e3a684a67946b7e3eed3e61a4
Source dataset
uspto-grants-2015_03
Patent number
US08980276B2

Reaction notes

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