Hydrochloric Acid → HCID 16019476, compound

HRID 624554Notes

Reaction equation

HRID 624554 reaction equation
[CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([S:9]([C:12]2[N:13]=[N:14][N:15]3[C:20]4[CH:21]=[CH:22][S:23][C:19]=4[C:18](=O)[NH:17][C:16]=23)(=[O:11])=[O:10])=[CH:5][CH:4]=1)[CH3:2].[S:25]1[CH:29]=[CH:28][CH:27]=[C:26]1[CH2:30][NH2:31].C1CCN2C(=NCCC2)CC1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.Cl.C([O-])([O-])=O.[Na+].[Na+]>C(#N)C.C(Cl)(Cl)Cl>[CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([S:9]([C:12]2[N:13]=[N:14][N:15]3[C:20]4[CH:21]=[CH:22][S:23][C:19]=4[C:18]([NH:31][CH2:30][C:26]4[S:25][CH:29]=[CH:28][CH:27]=4)=[N:17][C:16]=23)(=[O:11])=[O:10])=[CH:5][CH:4]=1)[CH3:2]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 34005(2-Thienylmethyl)amineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 2724699PyBOPHCID 178436712HCID 178436712, compound

Product 1

HCID 16019476HCID 16019476, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

Pyrimidin-5-one 15m (560 mg, 1.55 mmol) was treated with 2-thiophenemethylamine (0.48 mL, 4.66 mmol, 3 equivalent), DBU (0.70 mL, 4.66 mmol, 3 equivalent) and PyBOP (2.43 g, 4.66 mmol, 3 equivalent) in anhydrous acetonitrile (5.1 mL), and placed in a microwave vessel. The mixture was heated in a microwave synthesizer at 100° C. for 30 min. The reaction mixture was treated with aqueous HCl (1 M, 20 mL) and stirred for 30 min before Na2CO3 was added to adjust pH to approximately 9. The reaction mixture was dissolved in CHCl3 (75 mL), washed with aqueous HCl (1 M, 3×75 mL). The organic product layer was concentrated in vacuo and UTBinh-14 was purified by flash column chromatography: dichloromethane+1% acetic acid→dichloromethane:methanol (100:1+1% acetic acid). The residue was re-crystallized from ethanol to yield UTBinh-14 (392 mg, 55% yield) as a white solid. 1H NMR (CDCl3, 500 MHz): δ 1.21 (t, 3H, J=10 Hz), 2.67 (q, 2H, J=10 Hz), 5.15 (d, 2H, J=5 Hz), 5.86 (t, 1H, J=5 Hz), 7.01 (dd, 1H, J=5 Hz), 7.23 (d, 1H, J=5 Hz), 7.26 (d, 1H, J=5 Hz), 7.28 (d, 2H, J=5 Hz), 7.88 (d, 1H, J=5 Hz), 7.95 (d, 1H, J=5 Hz), 8.12 (d, 2H, J=10 Hz). 13C NMR (CDCl3, 125 Hz): δ 15.73, 29.55, 41.04, 118.13, 126.42, 127.89, 128.07, 128.64, 129.08, 133.84, 153.22. HR-ESI-MS (M+H)+ calc 456.0622. found 456.0583 for C20H17N5O2S3.

Workup

  1. customplaced in a microwave vessel
  2. additionwas added
  3. washwashed with aqueous HCl (1 M, 3×75 mL)
  4. concentrationThe organic product layer was concentrated in vacuo and UTBinh-14
  5. customwas purified by flash column chromatography
  6. customThe residue was re-crystallized from ethanol
  7. customto yield UTBinh-14 (392 mg, 55% yield) as a white solid

Sources & evidence

ORD record
ord-dde1e3c8c62a4e5e9fd7f6a90b8a5bcb
Source dataset
uspto-grants-2016_04
Patent number
US09303042B2

Reaction notes

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