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Benzenesulfonyl chloride → {1-[1'-Benzenesulfonyl-5-(4'-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-biphenyl-4-yl)-1',2',4',5'-tetrahydro-1H-[2,4']biimidazolyl-3'-carbonyl]-2-methyl-propyl]-carbamic acid methyl ester

HRID 79763
Notes
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Reaction equation

HRID 79763 reaction equation
[CH3:1][O:2][C:3](=[O:37])[NH:4][CH:5]([C:9]([N:11]1[CH:15]([C:16]2[NH:17][CH:18]=[C:19]([C:21]3[CH:26]=[CH:25][C:24](Br)=[CH:23][CH:22]=3)[N:20]=2)[CH2:14][N:13]([S:28]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)(=[O:30])=[O:29])[CH2:12]1)=[O:10])[CH:6]([CH3:8])[CH3:7].COC(=O)NC(C(N1C(C2NC=C(C3C=CC(Br)=CC=3)N=2)CN(C(=O)C)C1)=O)C(C)C.C1(S(Cl)(=O)=O)C=CC=CC=1.[CH3:79][O:80][C:81](=[O:114])[NH:82][CH:83]([C:87]([N:89]1[CH2:93][CH2:92][CH2:91][CH:90]1[C:94]1[NH:95][CH:96]=[C:97]([C:99]2[CH:104]=[CH:103][C:102](B3OC(C)(C)C(C)(C)O3)=[CH:101][CH:100]=2)[N:98]=1)=[O:88])[CH:84]([CH3:86])[CH3:85].C(=O)([O-])[O-].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.COCCOC>[CH3:1][O:2][C:3](=[O:37])[NH:4][CH:5]([C:9]([N:11]1[CH:15]([C:16]2[NH:20][C:19]([C:21]3[CH:26]=[CH:25][C:24]([C:102]4[CH:103]=[CH:104][C:99]([C:97]5[NH:98][C:94]([CH:90]6[CH2:91][CH2:92][CH2:93][N:89]6[C:87](=[O:88])[CH:83]([NH:82][C:81]([O:80][CH3:79])=[O:114])[CH:84]([CH3:86])[CH3:85])=[N:95][CH:96]=5)=[CH:100][CH:101]=4)=[CH:23][CH:22]=3)=[CH:18][N:17]=2)[CH2:14][N:13]([S:28]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)(=[O:30])=[O:29])[CH2:12]1)=[O:10])[CH:6]([CH3:8])[CH3:7]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

9

Reactant 5

HCID 7369Benzenesulfonyl chlorideHCID 11430Potassium CarbonateHCID 178502159HCID 178502159, compoundHCID 178502205HCID 178502205, compoundHCID 178502209HCID 178502209, compound

Product 1

HCID 66620333
{1-[1'-Benzenesulfonyl-5-(4'-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-biphenyl-4-yl)-1',2',4',5'-tetrahydro-1H-[2,4']biimidazolyl-3'-carbonyl]-2-methyl-propyl]-carbamic acid methyl ester
Yield 0%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

{1-[1′-Benzenesulfonyl-4-(4-bromo-phenyl)-1′,2′,4′,5′-tetrahydro-1H-[2,4′]biimidazolyl-3′-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester (63.1 mg, 106.9 mmol) [prepared as described for the synthesis of {1-[1′-Acetyl-4-(4-bromo-phenyl)-1′,2′,4′,5′-tetrahydro-1H-[2,4′]biimidazolyl-3′-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester (Example BY)] substituting the acetic anhydride with phenyl sulfonyl chloride] was combined with [2-Methyl-1-(2-{4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-propyl]-carbamic acid methyl ester (53.1 mg, 106.9 mmol) under an argon atmosphere. Potassium carbonate (29.2 mg, 0.212 mmol) and Pd(PPh3)4 (12.2 mg, 0.0106 mmol) were added, followed by DME (2.5 mL) and water (0.8 mL). The mixture was heated under microwave conditions for 20 minutes at 120° C. All volatiles were removed in vacuo and the crude material was dissolved in DMF and purified via RP-HPLC (eluent: water/MeCN w 0.1% TFA) to yield the product {1-[1′-Benzenesulfonyl-5-(4′-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-biphenyl-4-yl)-1′,2′,4′,5′-tetrahydro-1H-[2,4′]biimidazolyl-3′-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester (27.9 mg): LCMS-ESI+: calc'd for C45H53N9O8S: 880.2 (M+). Found: 881.5 (M+H+); 1H-NMR: 300 MHz, (MeOH-d4) δ: 8.01 (d, J=7.5 Hz, 2H), 7.90-7.76 (m, 11H), 7.65 (t, J=7.8 Hz, 2H), 5.59 (d, J=8.7 Hz, 1H), 5.25 (dd, J=7.5, 7.5 Hz, 1H), 5.19 (d, J=8.7 Hz, 1H), 4.67 (dd, J=7.5, 7.5 Hz, 1H), 4.32-4.22 (m, 2H), 4.08 (m, 2H), 3.85 (m, 1H), 3.68 (s, 3H), 3.66 (s, 3H), 3.44 (d, J=6.6 Hz, 1H), 2.57 (m, 1H), 2.29-1.99 (m, 5H), 0.99-0.86 (m, 12H).

Workup

  1. customAll volatiles were removed in vacuo
  2. dissolutionthe crude material was dissolved in DMF
  3. custompurified via RP-HPLC (eluent: water/MeCN w 0.1% TFA)

Sources & evidence

ORD record
ord-1bff54d51a8d4c29b62697d8214da80d
Source dataset
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08841278B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes