2,6-Lutidine → HCID 21886737, compound

HRID 2216041Notes

Reaction equation

HRID 2216041 reaction equation
C(OC(=O)NC(C1SC(SC)=C(S(C2C=C(C3C(C)=CC=CC=3N)C=CC=2)(=O)=O)C=1)=N)(C)(C)C.BrCC(OC(C)(C)C)=O.C(=O)([O-])[O-].[K+].[K+].N1C(C)=CC=CC=1C.CCN(CC)CC.C([O:69][C:70](=[O:106])[CH2:71][NH:72][C:73]1[CH:78]=[CH:77][CH:76]=[C:75]([CH3:79])[C:74]=1[C:80]1[CH:85]=[CH:84][CH:83]=[C:82]([S:86]([C:89]2[CH:93]=[C:92]([C:94]([NH:96]C(OC(C)(C)C)=O)=[NH:95])[S:91][C:90]=2[S:104][CH3:105])(=[O:88])=[O:87])[CH:81]=1)(C)(C)C>CCOC(C)=O.C1(C)C=CC=CC=1>[C:94]([C:92]1[S:91][C:90]([S:104][CH3:105])=[C:89]([S:86]([C:82]2[CH:81]=[C:80]([C:74]3[C:75]([CH3:79])=[CH:76][CH:77]=[CH:78][C:73]=3[NH:72][CH2:71][C:70]([OH:106])=[O:69])[CH:85]=[CH:84][CH:83]=2)(=[O:88])=[O:87])[CH:93]=1)(=[NH:95])[NH2:96]

Participants

9

Reactant 6

HCID 79372,6-LutidineHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 79177tert-Butyl bromoacetateHCID 145857623tert-butyl N-[4-[3-(2-amino-6-methylphenyl)phenyl]sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamateHCID 145857692HCID 145857692, compound

Product 1

HCID 21886737HCID 21886737, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

{[4-(2′-Amino-6′-methyl-biphenyl-3-sulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester (75 mg, 0.15 mmol, Example 25: step c), tert-butyl bromoacetate (43 μL, 0.29 mmol), potassium carbonate (29 mg, 0.21 mmol) and 2,6-lutidine (33 μL, 0.29 mmol) were dissolved into toluene (2 mL). The reaction was stirred and heated to 80° C. for 12 hours. Et3N (41 μL, 0.3 mmol) was added to reaction and heated to 80° C. for another 12 hours. The reaction mixture was dissolved into EtOAc and washed with brine. The organic layers were dried (MgSO4), the solvents were removed in vacuo followed purified by preparative SiO2 TLC purification (20% MeOH in DCM) resulting in {3′-[5-(tert-Butoxycarbonylamino-imino-methyl)-2-methylsulfanyl-thiophene-3-sulfonyl]-6-methyl-biphenyl-2-ylamino}-acetic acid tert-butyl ester. ESI-MS (m/z): Calcd. for C30H37N3O6S3: 632.2 (M+1) found: 631.9. {3′-[5-(tert-Butoxycarbonylamino-imino-methyl)-2-methylsulfanyl-thiophene-3-sulfonyl]-6-methyl-biphenyl-2-ylamino}-acetic acid tert-butyl ester was deprotected and purified as Example 1: step d, yielding the title compound as brown solid (1.7 mg). 1H-NMR (CD3OD): δ 8.35 (s, 1H), 8.08–8.06 (d, 1H, J=8.83 Hz), 7.77 (t, 1H, J=7.44 Hz, J=7.67 Hz), 7.63–7.61 (d, 1H, J=7.67 Hz), 7.16 (t, 1H, J=7.91 Hz, J=7.91 Hz), 7.05–6.68 (d, 2H, J=7.67 Hz), 6.52–6.50 (d, 1H, J=8.14 Hz), 3.81 (s, 1H), 2.72 (s, 3H), 2.17 (s, 3H). ESI-MS (m/z): Calcd. for C21H21N3O4S3: 476.1 (M+1); found: 476.1.

Workup

  1. temperatureheated to 80° C. for another 12 hours
  2. washwashed with brine
  3. dry with materialThe organic layers were dried (MgSO4)
  4. customthe solvents were removed in vacuo
  5. customfollowed purified by preparative SiO2 TLC purification (20% MeOH in DCM)
  6. customresulting in {3′-[5-(tert-Butoxycarbonylamino-imino-methyl)-2-methylsulfanyl-thiophene-3-sulfonyl]-6-methyl-biphenyl-2-ylamino}-acetic acid tert-butyl ester
  7. custompurified as Example 1: step d

Sources & evidence

ORD record
ord-76d0611324a4489db96ae9a13531631a
Source dataset
uspto-grants-2006_09
Patent number
US07109354B2

Reaction notes

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