Methyl chloroformate → HCID 89533800, compound

HRID 920238Notes

Reaction equation

HRID 920238 reaction equation
[NH2:1][CH:2]1[CH2:11][C:10]2[C:9]([CH2:12][N:13]3[C:17]4[CH:18]=[C:19]([F:31])[C:20]([S:22]([NH:25][C:26]5[S:30][N:29]=[CH:28][N:27]=5)(=[O:24])=[O:23])=[CH:21][C:16]=4[O:15][C:14]3=[O:32])=[CH:8][CH:7]=[CH:6][C:5]=2[CH2:4][CH2:3]1.CN1C(=O)CCC1.CCN(C(C)C)C(C)C.Cl[C:50]([O:52][CH3:53])=[O:51]>CO.O.CS(C)=O>[S:30]1[C:26]([NH:25][S:22]([C:20]2[C:19]([F:31])=[CH:18][C:17]3[N:13]([CH2:12][C:9]4[CH:8]=[CH:7][CH:6]=[C:5]5[C:10]=4[CH2:11][CH:2]([NH:1][C:50](=[O:51])[O:52][CH3:53])[CH2:3][CH2:4]5)[C:14](=[O:32])[O:15][C:16]=3[CH:21]=2)(=[O:24])=[O:23])=[N:27][CH:28]=[N:29]1

Participants

7

Reactant 4

HCID 6586Methyl chloroformateHCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 89524799HCID 89524799, compound

Product 1

HCID 89533800HCID 89533800, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 23503278(Methanesulfinyl)methane--water (1/1)Solvent

Procedure

To a vial was added a single enantiomer (R or S) of 3-((7-amino-5,6,7,8-tetrahydronaphthalen-1-yl)methyl)-5-fluoro-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (20-4) (19 mg, 0.037 mmol), then NMP (0.6 ml), DIPEA (30 μL, 0.172 mmol), and finally METHYL CHLOROFORMATE (12.30 μL, 0.159 mmol). The reaction mixture was then capped (not under N2) & stirred at room temperature. Followed by LC/MS. After 10 min at room temperature the reaction mixture was diluted with MeOH/drops of H2O/DMSO, then purified (without workup) by reverse phase chromatography (5-95% MeCN/H2O; 0.1% TFA in AQ; 20 min gradient; Waters 30×150 mm Sunfire 5 micron C18 column); desired fractions concentrated (GENEVAC), then dissolved in MeOH/DCM & concentrated to yield methyl (8-((6-(N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-5-fluoro-2-oxobenzo[d]oxazol-3(2H)-yl)methyl)-1,2,3,4-tetrahydronaphthalen-2-yl)carbamate (23-1). HRMS [M+H] calculated; 534.0912, observed; 534.0918. 1H NMR (499 MHz, DMSO): δ 8.48 (s, 1H); 7.79 (d, J=5.5 Hz, 1H); 7.33-7.23 (m, 2H); 7.08-7.03 (m, 2H); 6.88-6.82 (m, 1H); 5.75 (s, 1H); 5.03-4.91 (m, 2H); 3.81-3.71 (m, 2H); 3.55 (s, 3H); 3.06-2.99 (m, 1H); 2.87-2.80 (m, 2H); 1.95-1.88 (m, 1H); 1.68-1.57 (m, 1H).

Workup

  1. customThe reaction mixture was then capped (not under N2) &
  2. custompurified (without workup) by reverse phase chromatography (5-95% MeCN/H2O; 0.1% TFA in AQ; 20 min gradient; Waters 30×150 mm Sunfire 5 micron C18 column)
  3. concentrationdesired fractions concentrated (GENEVAC)
  4. dissolutiondissolved in MeOH/DCM
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-413ca9c307b94ee8b78bc1d70116bd18
Source dataset
uspto-grants-2016_03
Patent number
US09273040B2

Reaction notes

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