Dimethylformamide → (S)-2-amino-N-(4-(3-(piperidin-4-yloxy)phenyl)but-3-ynyl)pent-4-ynamide

HRID 473520Notes

Reaction equation

HRID 473520 reaction equation
[C:1]1([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:6]=[CH:5][CH:4]=C(C#CCCCN)C=1.C(OC([NH:26][CH:27]([CH2:31][C:32]#[CH:33])[C:28]([OH:30])=O)=O)(C)(C)C.C1C=CC2N(O)N=NC=2C=1.CC[N:46]=C=NCCCN(C)C.Cl.CC[N:58]([CH:62]([CH3:64])C)[CH:59]([CH3:61])C.CN([CH:68]=[O:69])C>>[NH2:26][C@@H:27]([CH2:31][C:32]#[CH:33])[C:28]([NH:46][CH2:4][CH2:5][C:6]#[C:1][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]([O:69][CH:68]2[CH2:61][CH2:59][NH:58][CH2:62][CH2:64]2)[CH:18]=1)=[O:30]

Participants

7

Reactant 6

HCID 6228DimethylformamideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 35131712-((Tert-butoxycarbonyl)amino)pent-4-ynoic acidHCID 672035705-(Biphenyl-3-yl)pent-4-yn-1-amine

Product 1

HCID 52919716(S)-2-amino-N-(4-(3-(piperidin-4-yloxy)phenyl)but-3-ynyl)pent-4-ynamide

Procedure

5-(Biphenyl-3-yl)pent-4-yn-1-amine (0.040 g, 0.17 mmol), 2-tert-Butoxycarbonylamino-pent-4-ynoic acid (40 mg, 0.19 mmol), HOBt (28 mg, 0.21 mmol), EDCl (40 mg, 0.21 mmol), and DIEA (0.044 mL, 0.25 mmol) were taken into DMF (3 mL) and stirred at room temperature overnight. The reaction was then quenched with water and the resulting mixture extracted with EtOAc. The organic layer was washed with saturated NaHCO3 and brine, then dried over sodium sulfate and the solvent removed in vacuo. The resulting residue was taken up into DCM/TFA (4/1, 5 mL) and the resulting mixture was stirred at room temp for 1 hr. The solvent was removed in vacuo and prepped on the Gilson HPLC to yield the title compound, as its corresponding TFA salt. MH+ 331.2; 1H NMR (300 MHz, DMSO): δ 1.6-1.8 (m, 3H), 2.45 (m, 2H), 2.7 (s, 2H), 3.2-3.4 (m, 2H), 3.9 (s, 1H), 7.3-7.4 (m, 5H), 7.6-7.7 (m, 4H), 8.3 (s, 2H), 8.6 (s, 1H)

Workup

  1. customThe reaction was then quenched with water
  2. extractionthe resulting mixture extracted with EtOAc
  3. washThe organic layer was washed with saturated NaHCO3 and brine
  4. dry with materialdried over sodium sulfate
  5. customthe solvent removed in vacuo
  6. stirringthe resulting mixture was stirred at room temp for 1 hr
  7. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-50428b495bf34bde8b4bf5df23e3e766
Source dataset
uspto-grants-2014_01
Patent number
US08633322B2

Reaction notes

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