1,2-Dichloroethane → HCID 71556486, compound

HRID 920237Notes

Reaction equation

HRID 920237 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.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.[C:47](O)(=[O:49])[CH3:48].CCN(C(C)C)C(C)C>CO.O.CN1C(=O)CCC1>[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:47](=[O:49])[CH3:48])[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

9

Reactant 5

HCID 111,2-DichloroethaneHCID 176Acetic AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 89524799HCID 89524799, compound

Product 1

HCID 71556486HCID 71556486, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a flask was added a single enantiomer (S or R) 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 (obtained through chiral separation of racemic 20-4) (15 mg, 0.029 mmol), then anhydrous HOBT (5.15 mg, 0.038 mmol), EDC (7.30 mg, 0.038 mmol), followed by NMP (1 ml), then ACETIC ACID (2.180 μl, 0.038 mmol) then DIPEA (0.025 ml, 0.143 mmol). The reaction mixture was stirred at room temperature (capped but not under N2) & followed by LC/MS for the disappearance of starting amine. The reaction mixture was diluted with MeOH/drops of H2O, was filtered (syringe filter), concentrated to desired volume (blow station) & submitted downstairs for mass guided reverse phase purification (TFA modifier); desired fractions concentrated to yield N-(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)acetamide (22-1, S or R). HRMS [M+H] calculated; 518.0963, observed; 518.0937. 1H NMR (499 MHz, DMSO): presaturation at 3.35 ppm: δ 8.49 (s, 1H); 7.96 (d, J=7.5 Hz, 1H); 7.80 (d, J=5.4 Hz, 1H); 7.29 (d, J=9.6 Hz, 1H); 7.06 (d, J=4.5 Hz, 2H); 6.85-6.81 (m, 1H); 5.02-4.91 (m, 2H); 4.06-3.95 (m, 1H); 3.05-2.99 (m, 1H); 2.86-2.80 (m, 2H); 2.53-2.48 (m, 1H); 1.95-1.85 (m, 1H); 1.82 (s, 3H); 1.68-1.58 (m, 1H).

Workup

  1. customcapped but not under N2) &
  2. filtrationwas filtered
  3. filtration(syringe filter)
  4. concentrationconcentrated to desired volume (blow station)
  5. customreverse phase purification (TFA modifier)
  6. concentrationdesired fractions concentrated

Sources & evidence

ORD record
ord-aa06dd0602e44a63b45a9259d2cedb2d
Source dataset
uspto-grants-2016_03
Patent number
US09273040B2

Reaction notes

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