4-Methylmorpholine → 4-(2'-Methyl-6'-morpholin-4-ylmethyl-biphenyl-3-sulfonyl)-5-methylsulfanyl-thiophene-2-carboxamidine

HRID 723256Notes

Reaction equation

HRID 723256 reaction equation
CS(Cl)(=O)=O.C(OC(=O)[NH:12][C:13]([C:15]1[S:16][C:17]([S:38][CH3:39])=[C:18]([S:20]([C:23]2[CH:24]=[C:25]([C:29]3[C:34]([CH2:35]O)=[CH:33][CH:32]=[CH:31][C:30]=3[CH3:37])[CH:26]=[CH:27][CH:28]=2)(=[O:22])=[O:21])[CH:19]=1)=[NH:14])(C)(C)C.C(N(C(C)C)CC)(C)C.C[N:51]1[CH2:56][CH2:55][O:54][CH2:53][CH2:52]1>C(Cl)Cl>[CH3:37][C:30]1[CH:31]=[CH:32][CH:33]=[C:34]([CH2:35][N:51]2[CH2:56][CH2:55][O:54][CH2:53][CH2:52]2)[C:29]=1[C:25]1[CH:26]=[CH:27][CH:28]=[C:23]([S:20]([C:18]2[CH:19]=[C:15]([C:13]([NH2:12])=[NH:14])[S:16][C:17]=2[S:38][CH3:39])(=[O:21])=[O:22])[CH:24]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 145857676tert-butyl N-[4-[3-[2-(hydroxymethyl)-6-methylphenyl]phenyl]sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamate

Product 1

HCID 218864384-(2'-Methyl-6'-morpholin-4-ylmethyl-biphenyl-3-sulfonyl)-5-methylsulfanyl-thiophene-2-carboxamidine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Methanesulfonyl chloride (100 μL) was added over 1 min to a 0° C. solution of {[4-(6′-hydroxymethyl-2′-methyl-biphenyl-3-sulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester (Example 5: step c) (30 mg)) and diisopropylethylamine (0.25 mL) in DCM (10 mL). The solution was stirred for 1 h at 0° C. and warmed to rt. 4-Methylmorpholine (0.5 mL) was added and the solution was stirred for 3 h at rt. The volatile components were removed in vacuo and the residue was treated with 1:1 TFA/DCM (10 mL) for 2 h at rt. The solvent was removed in vacuo and the residue was purified by preparative HPLC (C18-column, 10–70% CH3CN over 30 min) which yielded the title compound as a opaque glass (6.8 mg). 1H-NMR (CD3OD): δ 8.40 (s, 1H), 8.13 (ddd, 1H, J=1.2, 1.9, 7.9 Hz), 7.97 (t, 1H, J=1.6 Hz), 7.82 (t, 1H, J=7.9 Hz), 7.61 (m, 2H), 7.49 (m, 2H), 4.15 (d, 1H, J=13.5 Hz), 4.07 (d, 1H, J=13.5 Hz), 3.82 (br s, 4H), 2.75 (s, 3H), 2.18 (s, 2H), 2.03 (s, 3H), 1.31 (s, 2H). ESI-MS (m/z): Calcd. for C24H27N3O3S3 (M+H): 502.1; found: 502.1.

Workup

  1. temperaturewarmed to rt
  2. stirringthe solution was stirred for 3 h at rt
  3. customThe volatile components were removed in vacuo
  4. additionthe residue was treated with 1:1 TFA/DCM (10 mL) for 2 h at rt
  5. customThe solvent was removed in vacuo
  6. customthe residue was purified by preparative HPLC (C18-column, 10–70% CH3CN over 30 min) which

Sources & evidence

ORD record
ord-5b4fdd2deb414200aaccee6b1ce6e539
Source dataset
uspto-grants-2006_11
Patent number
US07138530B2

Reaction notes

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