Hydrochloric Acid → 2-(3-Oxo-2-thiophen-2-ylmethyl-2,3-dihydro-1H-isoindol-1-ylsulfanyl)-N-pyrimidin-2-yl-acetamide

HRID 2078471Notes

Reaction equation

HRID 2078471 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]([S:11][CH2:12][C:13]([OH:15])=O)[N:3]1[CH2:16][C:17]1[S:18][CH:19]=[CH:20][CH:21]=1.C(Cl)(=O)C(Cl)=O.[NH2:28][C:29]1[N:34]=[CH:33][CH:32]=[CH:31][N:30]=1.N1C=CC=CC=1.Cl>ClCCl.CN(C=O)C.C1COCC1>[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]([S:11][CH2:12][C:13]([NH:28][C:29]2[N:34]=[CH:33][CH:32]=[CH:31][N:30]=2)=[O:15])[N:3]1[CH2:16][C:17]1[S:18][CH:19]=[CH:20][CH:21]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 79782-AminopyrimidineHCID 65578Oxalyl chlorideHCID 36971622-[[3-oxo-2-(thiophen-2-ylmethyl)-1H-isoindol-1-yl]sulfanyl]acetic Acid

Product 1

HCID 166597422-(3-Oxo-2-thiophen-2-ylmethyl-2,3-dihydro-1H-isoindol-1-ylsulfanyl)-N-pyrimidin-2-yl-acetamideYield 41%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of compound 15 (200 mg, 0.63 mmol) in dichloromethane (8 mL) at 0° C. was added oxalyl chloride (0.35 mL of a 2M solution in dichloromethane, 0.69 mmol) and catalytic DMF (5 drops) and the resulting reaction mixture was allowed to stir at 0 C for 10 minutes and then at room temperature for 20 minutes. Thereafter a mixture of 2-aminopyrimidine (132 mg, 1.39 mmol) and pyridine (0.11 mL, 1.39 mmol) in THF (2 mL) was added to the reaction mixture and was allowed to stir at room temperature for 4 hours. The reaction mixture was poured onto 1N HCl and extracted with ethyl acetate (3×20 mL). The combined ethyl extracts were dried over anhydrous sodium sulfate and dried in vacuo. Chromatography (SiO2, 20 to 70% EtOAc-Hexanes eluant) provided 70 mg of 16 as a white solid. (170 mg theoretical, 41% yield). 1H NMR (300 MHz, DMSO): δ 10.55 (br s, 1H), 8.5 (d, J=3 Hz, 2H), 7.75-7.6 (m, 3H), 7.5 (m, 1H), 7.4 (m, 1H), 7.2-7.05 (m, 2H), 7.0-6.9 (m, 1H), 5.75 (s, 1HO, 5.15 (d, J=15 Hz, 1HO, 4.65 (d, J=15 Hz, 1H), 3.3 (d, J=15 Hz, 1H), 3.1 (d, J=15 Hz, 1H). MS: m/z (MH+) 397.

Workup

  1. customthe resulting reaction mixture
  2. waitat room temperature for 20 minutes
  3. additionwas added to the reaction mixture
  4. stirringto stir at room temperature for 4 hours
  5. extractionextracted with ethyl acetate (3×20 mL)
  6. dry with materialThe combined ethyl extracts were dried over anhydrous sodium sulfate
  7. customdried in vacuo

Sources & evidence

ORD record
ord-46fc456cfae741f7bc4ea3b3c9ecc383
Source dataset
uspto-grants-2011_04
Patent number
US07928246B2

Reaction notes

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