Dimethylformamide → HCID 53378459, compound

HRID 1620428Notes

Reaction equation

HRID 1620428 reaction equation
[H-].[Na+].[CH3:3][N:4]([CH3:7])[CH:5]=[O:6].[Cl:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[C@H:15]([N:20]1[CH2:25][CH2:24][CH:23]2[S:26][C:27](=[O:29])[CH:28]=[C:22]2[CH2:21]1)[C:16]([O:18][CH3:19])=[O:17].CN(C)C(Cl)=O>C(OCC)(=O)C.O>[CH3:3][N:4]([CH3:7])[C:5]([O:29][C:27]1[S:26][C:23]2[CH2:24][CH2:25][N:20]([C@@H:15]([C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=3[Cl:8])[C:16]([O:18][CH3:19])=[O:17])[CH2:21][C:22]=2[CH:28]=1)=[O:6]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 6598Dimethylcarbamoyl ChlorideHCID 24758Sodium hydrideHCID 56848893Methyl (2S)-(2-chlorophenyl)(2-oxo-2,6,7,7a-tetrahydrothieno[3,2-c]pyridin-5(4H)-yl)acetate

Product 1

HCID 53378459HCID 53378459, compoundYield 45%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

In an ice bath, sodium hydride (20 mg, 60%) were added to 6 ml of anhydrous N, N-dimethyl formamide, to which 169 mg of (2S)-methyl 2-(2-chlorophenyl)-2-(2-oxo-7,7a-dihydrothieno[3.2-c]pyridine-5(2H,4H,6H)-yl)-acetate (IV-1) was then added. The reaction was naturally warmed to room temperature, stirred for 1 hr, and then cooled to 0° C. 200 μl of N,N-dimethylcarbamoyl chloride was slowly added dropwise. The reaction was naturally warmed to room temperature, and stirred for 3 hrs, and at this time, TLC showed that the raw materials substantially disappeared. The reaction solution was poured into water (30 ml), the aqueous phase was extracted with ethyl acetate (50 ml×3), and the organic phase was dried to obtain a crude product, which was subjected to flash column chromatography (petroleum ether:ethyl acetate=40:3), to obtain (S)-methyl 2-(2-(N,N-dimethylcarbamoyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate (I-18) (95 mg). Yield: 45%, mp 96-98° C., ee=93.5% (chiral HPLC analysis conditions were the same as those in Example 10), [α]D20=+34° (c 0.50, MeOH); 1H-NMR (500 MHz, CDCl3) δ 2.73-2.76 (m, 2H), 2.85-2.89 (m, 2H), 2.99 (s, 3H), 3.03 (s, 3H), 3.52 (d, 1H, J=14.3 Hz), 3.63 (d, 1H, J=14.3 Hz), 3.72 (s, 3H), 4.91 (s, 1H), 6.19 (s, 1H), 7.26-7.69 (m, 4H); 13C-NMR (75 MHz, CDCl3) δ 25.03, 36.37, 36.88, 48.18, 50.40, 52.12, 67.87, 111.48, 125.38, 127.12, 129.09, 129.37, 129.76, 129.95, 130.56, 133.80, 134.34, 134.68, 151.04, 171.27; ESI-MS m/z 409.2 [M+H]+; HRMS Calcd for C19H22N2O4SCl [M+H]+ m/z 409.0992. found 409.0989.

Workup

  1. additionwas then added
  2. temperaturecooled to 0° C
  3. temperatureThe reaction was naturally warmed to room temperature
  4. stirringstirred for 3 hrs
  5. extractionthe aqueous phase was extracted with ethyl acetate (50 ml×3)
  6. customthe organic phase was dried
  7. customto obtain a crude product, which

Sources & evidence

ORD record
ord-d2be8170e5644306ae32fcee8d74ff4c
Source dataset
uspto-grants-2014_07
Patent number
US08772489B2

Reaction notes

Loading…