Triethylamine → tert-butyl N-[4-[3-(4-methylpyrimidin-5-yl)phenyl]sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamate

HRID 2216191Notes

Reaction equation

HRID 2216191 reaction equation
Br[C:2]1[C:3]([CH3:8])=[N:4][CH:5]=[N:6][CH:7]=1.[C:9]([O:13][C:14](=[O:37])[NH:15][C:16]([C:18]1[S:19][C:20]([S:35][CH3:36])=[C:21]([S:23]([C:26]2[CH:31]=[CH:30][CH:29]=[C:28](B(O)O)[CH:27]=2)(=[O:25])=[O:24])[CH:22]=1)=[NH:17])([CH3:12])([CH3:11])[CH3:10].C([O-])([O-])=O.[Na+].[Na+].C(N(CC)CC)C.C([O-])(O)=O.[Na+]>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.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CCOC(C)=O.O1CCOCC1.C1(C)C=CC=CC=1.C(O)C>[C:9]([O:13][C:14](=[O:37])[NH:15][C:16](=[NH:17])[C:18]1[S:19][C:20]([S:35][CH3:36])=[C:21]([S:23]([C:26]2[CH:27]=[CH:28][CH:29]=[C:30]([C:2]3[C:3]([CH3:8])=[N:4][CH:5]=[N:6][CH:7]=3)[CH:31]=2)(=[O:25])=[O:24])[CH:22]=1)([CH3:12])([CH3:10])[CH3:11]

Participants

12

Reactant 5

HCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 516892Sodium BicarbonateHCID 124618635-Bromo-4-methylpyrimidineHCID 140043492[3-[5-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-2-methylsulfanylthiophen-3-yl]sulfonylphenyl]boronic acid

Product 1

HCID 145857624tert-butyl N-[4-[3-(4-methylpyrimidin-5-yl)phenyl]sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamateYield 87%

Reagents, catalysts & solvents 6

HCID 178418397HCID 178418397, compoundCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a flask with a reflux condenser under argon was added 5-Bromo-4-methyl-pyrimidine (9 mg, 0.044 mmol), prepared according to the procedure of Yamanaka, Sakamoto, Nishimura, and Sagi, Chem. Pharm. Bull. 35(8), 3119–3126 (1987). {[4-(3-dihydroxyboranyl-benzenesulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester (20 mg, 0.044 mmol, Example 140: step a), Na2CO3 (2M, 0.220 mL, 0.44 mmol), Pd(PPh3)4 (8 mg, 0.007 mmol), ethanol (0.220 mL) and toluene (0.440 mL). PdCl2(PPh3)2 (42 mg, 0.06 mmol), dioxane (4 mL), and triethylamine (420 μL, 3 mmol) and the mixture was stirred for 2 h 15 min at 90° C. After cooling to rt, EtOAc (2 mL) and NaHCO3 (saturated, 2 mL) were added and the layers were separated. The organic layer concentrated in vacuo followed by purification of the crude material by preparative TLC (5% methanol in dichloromethane) to yield the title compound (19 mg, 87%) as a white solid. 1H-NMR (CDCl3): δ 9.12 (s, 1H), 8.54 (s, 1H), 8.10–7.29 (m, 7H), 2.59 (s, 3H), 2.50 (s, 3H), 1.51 (s, 9H). ESI-MS (m/z): Calcd. for C22H24N4O4S3: 504.1 (M−BOC)+H; found: 405.1.

Workup

  1. customprepared
  2. customthe layers were separated
  3. concentrationThe organic layer concentrated in vacuo
  4. customfollowed by purification of the crude material by preparative TLC (5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-c8eede3438b94a79b08d74ddfdc49513
Source dataset
uspto-grants-2006_09
Patent number
US07109354B2

Reaction notes

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