2,6-Lutidine → N-((1R,2R)-2-(3-(4-(Hex-5-ynyloxy)phenyl)propylamino)-1,2-diphenylethyl)-4-methylbenzenesulfonamide

HRID 631756Notes

Reaction equation

HRID 631756 reaction equation
C([CH:3](O)[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17]#[CH:18])=[CH:8][CH:7]=1)C.N1C(C)=CC=CC=1C.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.[CH3:43][C:44]1[CH:49]=[CH:48][C:47]([S:50]([NH:53][C@@H:54]([C@H:61]([NH2:68])[C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=2)[C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)(=[O:52])=[O:51])=[CH:46][CH:45]=1.CCN(CC)CC>C(Cl)Cl>[CH2:13]([O:12][C:9]1[CH:8]=[CH:7][C:6]([CH2:5][CH2:4][CH2:3][NH:68][C@H:61]([C:62]2[CH:63]=[CH:64][CH:65]=[CH:66][CH:67]=2)[C@H:54]([NH:53][S:50]([C:47]2[CH:46]=[CH:45][C:44]([CH3:43])=[CH:49][CH:48]=2)(=[O:52])=[O:51])[C:55]2[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=2)=[CH:11][CH:10]=1)[CH2:14][CH2:15][CH2:16][C:17]#[CH:18]

Participants

7

Reactant 5

HCID 79372,6-LutidineHCID 8471TriethylamineHCID 67749Trifluoromethanesulfonic anhydrideHCID 2734565N-((1R,2R)-2-Amino-1,2-diphenylethyl)-4-methylbenzene-1-sulfonamideHCID 118434145Ethyl-3-(4-(hex-5-ynyloxy)phenyl)propan-1-ol

Product 1

HCID 90152985N-((1R,2R)-2-(3-(4-(Hex-5-ynyloxy)phenyl)propylamino)-1,2-diphenylethyl)-4-methylbenzenesulfonamideYield 82%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

This compound was prepared according to general procedure 5 using 3 ethyl-3-(4-(hex-5-ynyloxy)phenyl)propan-1-ol (400 mg, 1.72 mmol), 2,6-lutidine (353 mg, 3.30 mmol), trifluoromethanesulfonic anhydride (787 mg, 2.80 mmol), (R,R)-TsDPEN (403 mg, 1.10 mmol), Et3N (263 mg, 2.60 mmol) and DCM (8 cm3). The product was purified by column chromatography as in the general procedure. TLC: silica gel, 30% EtOAc in petroleum ether, product Rf=0.36 with visualisation by UV and KMnO4, 2,6-lutidine Rf=0.29 with visualisation by UV, 2,6-lutidine elutes with the product). The fractions containing the product were collected, combined and dried under reduced pressure to give a white solid. The solid was then washed with pentane to remove residual 2,6-lutidine. The mixture was filtered and the solid dried to give the product as a white solid (524 mg, 0.900 mmol, 82% based on 403 mg, 1.1 mmol N-(2-aminoethyl)-4-methylbenzenesulfonamide)). Mp 123-124° C.; [α]D27−25.2 (c 0.25 in CHCl3) (R,R); (found (ESI): M++H, 581.2833 C36H41N2O3S requires M, 581.2832); υmax 3286, 3248, 2915, 1510, 1454, 1434, 1316, 1242, 1160, 1031, 808, 700 cm−1; δH (400 MHz, CDCl3) 7.37 (2H, d, J 8.5 Hz, CHArSO2), 7.13-7.11 (3H, m, CHAr), 7.05-6.88 (12H, m, CHAr and NHSO2 overlapping), 6.78 (2H, d, J 8.5 Hz, CHArSO2), 6.28 (1H, br s, NH), 4.25 (1H, d, J 7.8 Hz, CHNSO2), 3.95 (2H, t, J 5.0 Hz, CH2OAr), 3.59 (1H, d, J 7.8 Hz, CHN), 2.51-2.38 (3H, m, ArCH2 and CH2N overlapping), 2.31 (3H, s, CH3), 2.29-2.24 (3H, m, HCCCH2 and CH2N overlapping), 1.96 (1H, t, J 2.6 Hz, HCCCH2), 1.92-1.85 (2H, m, CH2CH2CH2OAr), 1.75-1.61 (4H, m, CH2CH2N and HCCCH2CH2); δC (100 MHz, CDCl3) 157.20 (CAr), 142.70 (CAr), 139.33 (CAr), 138.39 (CAr), 137.09 (CAr), 133.79 (CAr), 129.21 (2 CHAr), 129.10 (2 CHAr), 128.31 (2 CHAr), 127.93 (2 CHAr), 127.58 (2 CHAr), 127.46 (CHAr), 127.41 (2 CHAr), 127.29 (CHAr), 127.13 (2 CHAr), 114.39 (2 CHAr) 84.18 (C), 68.64 (CH), 67.77 (CH), 67.29 (CH2), 63.09 (CH), 46.45 (CH2), 32.37 (CH2), 31.71 (CH2), 28.37 (CH2), 25.11 (CH2), 21.46 (CH3), 18.19 (CH2); m/z (ESI) 581.3 (M++1).

Workup

  1. customThis compound was prepared
  2. customThe product was purified by column chromatography as in the general procedure
  3. additionThe fractions containing the product
  4. customwere collected
  5. customdried under reduced pressure
  6. customto give a white solid
  7. washThe solid was then washed with pentane
  8. customto remove residual 2,6-lutidine
  9. filtrationThe mixture was filtered
  10. customthe solid dried

Sources & evidence

ORD record
ord-497466a2a84c4132866cf33d822d64f4
Source dataset
uspto-grants-2016_04
Patent number
US09321045B2

Reaction notes

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