Diisopropylethylamine → (S)-1-{5'-[(1-Benzo[1,3]dioxol-5-yl-cyclopropanecarbonyl)-amino]-2'-methyl-biphenyl-4-sulfonyl}-pyrrolidine-2-carboxylic acid

HRID 39182Notes

Reaction equation

HRID 39182 reaction equation
[NH:1]1[CH2:8][CH2:7][CH2:6][C@H:2]1[C:3]([OH:5])=[O:4].C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C.[O:21]1[C:25]2[CH:26]=[CH:27][C:28]([C:30]3([C:33]([NH:35][C:36]4[CH:37]=[CH:38][C:39]([CH3:52])=[C:40]([C:42]5[CH:47]=[CH:46][C:45]([S:48](Cl)(=[O:50])=[O:49])=[CH:44][CH:43]=5)[CH:41]=4)=[O:34])[CH2:32][CH2:31]3)=[CH:29][C:24]=2[O:23][CH2:22]1.CCN(C(C)C)C(C)C>O1CCOCC1>[O:21]1[C:25]2[CH:26]=[CH:27][C:28]([C:30]3([C:33]([NH:35][C:36]4[CH:37]=[CH:38][C:39]([CH3:52])=[C:40]([C:42]5[CH:47]=[CH:46][C:45]([S:48]([N:1]6[CH2:8][CH2:7][CH2:6][C@H:2]6[C:3]([OH:5])=[O:4])(=[O:49])=[O:50])=[CH:44][CH:43]=5)[CH:41]=4)=[O:34])[CH2:32][CH2:31]3)=[CH:29][C:24]=2[O:23][CH2:22]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 145742L-ProlineHCID 6913588N,O-bis(trimethylsilyl)acetamideHCID 59205984HCID 59205984, compound

Product 1

HCID 59206025(S)-1-{5'-[(1-Benzo[1,3]dioxol-5-yl-cyclopropanecarbonyl)-amino]-2'-methyl-biphenyl-4-sulfonyl}-pyrrolidine-2-carboxylic acid

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

L-Proline (57 mg, 0.50 mmol) was treated with N,O-bis(trimethylsilyl)acetamide (250 μL, 1.0 mmol) in 1 mL dioxane overnight at 50° C. To this mixture was added 5′-(1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-2′-methylbiphenyl-4-sulfonyl chloride (˜35 μmol, 400 μl solution in chloroform) followed by DIEA (100 μl). The reaction mixture was kept at room temperature for 1 h, evaporated, and diluted with DMSO (400 μl). The resulting solution was subjected to preparative HPLC purification. Fractions containing the desired material were combined and concentrated in vacuum centrifuge at 40° C. to provide the trifluoroacetic salt of (S)-1-{5′-[(1-Benzo[1,3]dioxol-5-yl-cyclopropanecarbonyl)-amino]-2′-methyl-biphenyl-4-sulfonyl}-pyrrolidine-2-carboxylic acid. ESI-MS m/z calc. 548.1, found 549.1 (M+1), retention time 3.40 min; 1H NMR (250 MHz, DMSO-d6) δ 1.04 (m, 2H), δ 1.38 (m, 2H), δ 1.60 (m, 1H), δ 1.80-1.97 (m, 3H) δ 2.16 (s, 3H), δ 3.21 (m, 1H), 3.39 (m, 1H), 4.15 (dd, 1H, J=4.1 Hz, J=7.8 Hz), δ 6.01 (s, 2H), δ 6.89 (s, 2H), δ 6.98 (s, 1H), δ 7.21 (d, 1H, J=8.3 Hz), δ 7.45 (d, 1H, J=2 Hz), δ 7.52 (dd, 1H, J=2 Hz, J=8.3 Hz), δ 7.55 (d, 2H, J=8.3 Hz), δ 7.88 (d, 2H, J=8.3 Hz), δ 8.80 (s, 1H).

Workup

  1. customevaporated
  2. additiondiluted with DMSO (400 μl)
  3. customThe resulting solution was subjected to preparative HPLC purification
  4. additionFractions containing the desired material
  5. concentrationconcentrated in vacuum centrifuge at 40° C.

Sources & evidence

ORD record
ord-ed4a4b7466ca4d308afc9f563d4124d3
Source dataset
uspto-grants-2013_09
Patent number
US08524767B2

Reaction notes

Loading…