Trimethyl borate → HCID 140043499, compound

HRID 723036Notes

Reaction equation

HRID 723036 reaction equation
C([Li])CCC.Br[C:7]1[C:8]([Cl:13])=[N:9][CH:10]=[CH:11][CH:12]=1.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]([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]([C:7]3[C:8]([Cl:13])=[N:9][CH:10]=[CH:11][CH:12]=3)[CH:39]=2)(=[O:37])=[O:36])[CH:34]=1)=[NH:29])([CH3:24])([CH3:23])[CH3:22]

Participants

10

Reactant 5

HCID 8470Trimethyl borateHCID 10340Sodium CarbonateHCID 6933243-Bromo-2-chloropyridineHCID 145857672tert-butyl N-[4-(3-bromophenyl)sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamate2×HCID 178418339Butyllithium

Product 1

HCID 140043499HCID 140043499, compoundYield 59.2%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
-78 °C

Procedure

Butyllithium (2.5 M, 1.0 mL, 2.5 mmol) was added dropwise to a −78° C. solution of 3-bromo-2-chloropyridine (384 mg, 2.0 mmol) in Et2O (10 mL). The solution was stirred at −78° C. for 1 h and trimethylborate (2.3 mL, 20 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 and the solid material was dried under high vacuum for 2 h. A portion of the crude solid (105 mg, 0.63 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 (31 mg, 58%) as a light-yellow glass.

Workup

  1. temperatureThe solution was warmed to rt over 15 min
  2. stirringstirred for 2 h at rt
  3. customThe volatile components were removed
  4. customthe solid material 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-19e943e9d14a45b09b6badc093cb768d
Source dataset
uspto-grants-2006_11
Patent number
US07138530B2

Reaction notes

Loading…