Sodium Carbonate → [3'-(5-Carbamimidoyl-2-methylsulfanyl-thiophene-3-sulfonyl)-6-methyl-biphenylylmethoxy]-acetic acid trifluoroacetate

HRID 2216209Notes

Reaction equation

HRID 2216209 reaction equation
C(OC(=O)[NH:7][C:8]([C:10]1[S:11][C:12]([S:25][CH3:26])=[C:13]([S:15]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20](Br)[CH:19]=2)(=[O:17])=[O:16])[CH:14]=1)=[NH:9])(C)(C)C.C([O:32][C:33](=[O:53])[CH2:34][O:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[C:39]([CH3:43])[C:38]=1B1OC(C)(C)C(C)(C)O1)(C)(C)C.C([O-])([O-])=O.[Na+].[Na+].[C:60]([OH:66])([C:62]([F:65])([F:64])[F:63])=[O:61].C(Cl)Cl>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.C1(C)C=CC=CC=1.C(O)C>[F:63][C:62]([F:65])([F:64])[C:60]([OH:66])=[O:61].[C:8]([C:10]1[S:11][C:12]([S:25][CH3:26])=[C:13]([S:15]([C:18]2[CH:19]=[C:20]([C:38]3[C:39]([CH3:43])=[CH:40][CH:41]=[CH:42][C:37]=3[CH2:36][O:35][CH2:34][C:33]([OH:53])=[O:32])[CH:21]=[CH:22][CH:23]=2)(=[O:17])=[O:16])[CH:14]=1)(=[NH:9])[NH2:7]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 21863450Trifluoroacetic acid methylene chlorideHCID 69586495[3-Methyl-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyloxy]-acetic acid tert-butyl esterHCID 145857672tert-butyl N-[4-(3-bromophenyl)sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamate

Product 1

HCID 69586335[3'-(5-Carbamimidoyl-2-methylsulfanyl-thiophene-3-sulfonyl)-6-methyl-biphenylylmethoxy]-acetic acid trifluoroacetateYield 22%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

The procedure used in Example 1: step c was followed using {[4-(3-bromo-benzenesulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester ((Example 27: step c) 123 mg, 0.25 mmol), [3-methyl-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyloxy]-acetic acid tert-butyl ester ((Example 299: step c) 270 mg, 0.75 mmol), Na2CO3 (2M, 1.5 mL, 3 mmol), Pd(PPh3)4 (66 mg, 0.06 mmol), ethanol (1.5 mL) and toluene (3 mL). Analogous aqueous workup yielded 417 mg of crude material which was treated with 1:1 TFA/DCM as described in Example 1: step d. Analogous purification by C18-HPLC yielded the title compound (26.8 mg, 22%) as a white solid. 1H-NMR (CD3OD): δ 8.35 (s, 1H), 8.07 (ddd, 1H, J=1.2, 1.9, 7.9 Hz), 7.86 (t, 1H, J=1.6 Hz), 7.71 (t, 1H, J=7.9 Hz), 7.10–7.43 (m, 3H), 4.25 (m, 2H), 4.07 (br s, 1H), 3.78 (br s, 1H), 2.73 (s, 3H), 2.35 (s, 3H), 2.02 (s, 3H). ESI-MS (m/z): Calcd. for C22H22N2O5S3 (M+H): 490.1; found: 490.1.

Workup

  1. customAnalogous aqueous workup yielded 417 mg of crude material which
  2. customAnalogous purification by C18-HPLC

Sources & evidence

ORD record
ord-4ee67528fedb4eabad4cd8f1cc351ba2
Source dataset
uspto-grants-2006_09
Patent number
US07109354B2

Reaction notes

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