Thiomorpholine → HCID 24801217, compound

HRID 386456Notes

Reaction equation

HRID 386456 reaction equation
[CH:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][C:17]([C:19]3[O:20][C:21]([C:24]4[N:29]=[C:28]([C:30]([O:32][CH3:33])=[O:31])[CH:27]=[CH:26][CH:25]=4)=[CH:22][N:23]=3)=[O:18])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1)=O.[NH:34]1[CH2:39][CH2:38][S:37][CH2:36][CH2:35]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClC(Cl)C>[S:37]1[CH2:38][CH2:39][N:34]([CH2:1][C:3]2[CH:8]=[CH:7][C:6]([C:9]3[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][C:17]([C:19]4[O:20][C:21]([C:24]5[N:29]=[C:28]([C:30]([O:32][CH3:33])=[O:31])[CH:27]=[CH:26][CH:25]=5)=[CH:22][N:23]=4)=[O:18])=[CH:11][CH:10]=3)=[CH:5][CH:4]=2)[CH2:35][CH2:36]1

Participants

5

Reactant 3

HCID 67164ThiomorpholineHCID 5049666Sodium triacetoxyborohydrideHCID 86645815HCID 86645815, compound

Product 1

HCID 24801217HCID 24801217, compoundYield 61%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

Methyl 6-(2-(3-(4′-formylbiphenyl-4-yl)propanoyl)oxazol-5-yl)pyridine-2-carboxylate (124 mg, 0.282 mmol) and thiomorpholine (0.040 mL, 0.42 mmol) were dissolved in dichloroethane (12 mL) and NaBH(OAc)3 (179 mg, 0.845 mmol) was added. The reaction solution was stirred under an atmosphere of Ar at ambient temperature for 3.5 h and then quenched with saturated aqueous NaHCO3. The crude product was extracted with EtOAc and the solvent was removed in vacuo. The crude product was purified by flash chromatography (SiO2, 50-90% EtOAc/hexanes) to furnish methyl 6-(2-(3-(4′-(thiomorpholinomethyl)biphenyl-4-yl)propanoyl)oxazol-5-yl)pyridine-2-carboxylate as a pale tan solid (90 mg, 61%): 1H NMR (CDCl3, 600 MHz) δ 8.12 (d, 1H, J=7.7 Hz), 8.04-8.02 (m, 2H), 7.97 (t, 1H, J=7.8 Hz), 7.52 (dd, 4H, J=8.2, 1.8 Hz), 7.35 (t, 4H, J=8.6 Hz), 4.03 (s, 3H), 3.55 (s, 2H), 3.51 (t, 2H, J=7.6 Hz), 3.16 (t, 2H, J=7.6 Hz), 2.74-2.73 (m, 4H), 2.70-2.68 (m, 4H); 13C NMR (CDCl3, 150 MHz) δ 187.3, 165.1, 157.4, 152.4, 148.5, 146.5, 139.7, 139.3, 139.0, 138.3, 137.0, 129.4, 128.9, 128.0, 127.1, 126.8, 125.2, 123.3, 63.3, 54.9, 53.0, 40.6, 29.3, 28.0; HR ESI-TOF m/z 528.1950 (M+H+, C30H29N3O4S, requires 528.1951).

Workup

  1. customquenched with saturated aqueous NaHCO3
  2. extractionThe crude product was extracted with EtOAc
  3. customthe solvent was removed in vacuo
  4. customThe crude product was purified by flash chromatography (SiO2, 50-90% EtOAc/hexanes)

Sources & evidence

ORD record
ord-699d60ea317f4101bf710267d8527b93
Source dataset
uspto-grants-2013_02
Patent number
US08372823B2

Reaction notes

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