Trimethyl borate → HCID 145857664, compound

HRID 2215988Notes

Reaction equation

HRID 2215988 reaction equation
C([Li])CCC.Br[C:7]1[CH:8]=[N:9][CH:10]=[CH:11][C:12]=1[CH3:13].COB(OC)OC.[C:21]([O:25][C:26](=[O:47])[NH:27][C:28]([C:30]1[S:31][C:32]([S:45][CH3:46])=[C:33]([S:35]([C:38]2[CH:43]=[CH:42][CH:41]=[C:40](Br)[CH:39]=2)(=[O:37])=[O:36])[CH:34]=1)=[NH:29])([CH3:24])([CH3:23])[CH3:22].C([O-])([O-])=O.[Na+].[Na+]>CCOCC.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>[C:21]([O:25][C:26](=[O:47])[NH:27][C:28](=[NH:29])[C:30]1[S:31][C:32]([S:45][CH3:46])=[C:33]([S:35]([C:38]2[CH:39]=[CH:40][CH:41]=[C:42]([C:7]3[CH:8]=[N:9][CH:10]=[CH:11][C:12]=3[CH3:13])[CH:43]=2)(=[O:37])=[O:36])[CH:34]=1)([CH3:24])([CH3:22])[CH3:23]

Participants

10

Reactant 5

HCID 8470Trimethyl borateHCID 10340Sodium CarbonateHCID 8176303-Bromo-4-methylpyridineHCID 145857672tert-butyl N-[4-(3-bromophenyl)sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamate2×HCID 178418339Butyllithium

Product 1

HCID 145857664HCID 145857664, compoundYield 71.5%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
-78 °C

Procedure

Butyllithium (2.5 M, 1.88 mL, 4.5 mmol) was added dropwise to a −78° C. solution of 3-bromo-4-methylpyridine (645 mg, 3.75 mmol) in Et2O (15 mL). The solution was stirred at −78° C. for 1 h and trimethylborate (5 mL, 44 mmol) was added in one portion. The solution was warmed to rt over 15 min and stirred for 2 h at rt . The volatile components were removed in vacuo and the solid residue was dried under high vacuum for 2 h. A portion of the crude solid (81 mg, 0.4 mmol) was reacted with {[4-(3-bromo-benzenesulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester (Example 27 (50 mg, 0.1 mmol)), Pd(PPh3)4 (29 mg, 0.025 mmol), Na2CO3 (2M, 0.8 mL, 1.6 mmol), ethanol (0.8 mL) and toluene (1.6 mL) according to the procedure used in Example 1: step c. Analogous aqueous workup and purification of the crude material by preparative TLC (50% EtOAc in hexanes) yielded the title compound (36 mg, 71%) as a light-yellow glass. 1H-NMR (CDCl3): δ 8.50 (d 1H, J=5.1 Hz), 8.42 (s, 1H), 8.07 (s, 1H), 7.99 (m, 2H), 7.45–7.70 (m, 5H), 7.24 (d, 1H, J=5.1 Hz), 2.59 (s, 3H), 2.27 (s, 3H), 1.52 (s, 9H). ESI-MS (m/z): Calcd. for C23H25N3O4S3: 503.7; found: 503.8.

Workup

  1. temperatureThe solution was warmed to rt over 15 min
  2. stirringstirred for 2 h at rt
  3. customThe volatile components were removed in vacuo
  4. customthe solid residue was dried under high vacuum for 2 h
  5. customAnalogous aqueous workup and purification of the crude material by preparative TLC (50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-1e014df7835241e89bc8f58e762548b6
Source dataset
uspto-grants-2006_09
Patent number
US07109354B2

Reaction notes

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