Sodium Bicarbonate → HCID 58293777, compound

HRID 446746Notes

Reaction equation

HRID 446746 reaction equation
[F:1][C:2]1[C:7]([F:8])=[C:6]([O:9][CH3:10])[CH:5]=[CH:4][C:3]=1[N:11]1[C:15]([C:16]2[C:17]([NH2:31])=[N:18][CH:19]=[C:20](B3OC(C)(C)C(C)(C)O3)[CH:21]=2)=[N:14][N:13]=[N:12]1.Br[C:33]1[S:37][C:36]([CH:38]2[CH2:43][CH2:42][N:41]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:40][CH2:39]2)=[C:35]([CH3:51])[CH:34]=1.C([O-])(O)=O.[Na+]>CN(C=O)C.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:31][C:17]1[N:18]=[CH:19][C:20]([C:33]2[S:37][C:36]([CH:38]3[CH2:39][CH2:40][N:41]([C:44]([O:46][C:47]([CH3:49])([CH3:48])[CH3:50])=[O:45])[CH2:42][CH2:43]3)=[C:35]([CH3:51])[CH:34]=2)=[CH:21][C:16]=1[C:15]1[N:11]([C:3]2[CH:4]=[CH:5][C:6]([O:9][CH3:10])=[C:7]([F:8])[C:2]=2[F:1])[N:12]=[N:13][N:14]=1

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 58293787HCID 58293787, compound2×HCID 58293850HCID 58293850, compound2×

Product 1

HCID 58293777HCID 58293777, compoundYield 84.8%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 3-(1-(2,3-difluoro-4-methoxyphenyl)-1H-tetrazol-5-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (Compound 1106, 200 mg, 0.4649 mmol) and tert-butyl 4-(5-bromo-3-methylthiophen-2-yl)piperidine-1-carboxylate (Compound 1054, 167.5 mg, 0.4650 mmol) in DMF (8 mL) was added a solution of NaHCO3 (2.509 g, 1.162 mL of 1.2 M, 1.395 mmol). The mixture was degassed under a nitrogen stream for 20 minutes. PdCl2(dppf) (34.02 mg, 0.04650 mmol) was added and the reaction was stirred for 10 minutes at 120° C. under microwave irradiation. The mixture was diluted with EtOAc, filtered, and the filtrate was washed with water. The organics were dried over magnesium sulfate, concentrated, and the resulting residue purified via silica gel chromatography to give tert-butyl 4-(5-(6-amino-5-(1-(2,3-difluoro-4-methoxyphenyl)-1H-tetrazol-5-yl)pyridin-3-yl)-3-methylthiophen-2-yl)piperidine-1-carboxylate (Compound 1107, 230 mg, 83%) as a yellow solid.

Workup

  1. customThe mixture was degassed under a nitrogen stream for 20 minutes
  2. filtrationfiltered
  3. washthe filtrate was washed with water
  4. dry with materialThe organics were dried over magnesium sulfate
  5. concentrationconcentrated
  6. customthe resulting residue purified via silica gel chromatography

Sources & evidence

ORD record
ord-1405775c6f684bedae4a76f7e3c9e9bb
Source dataset
uspto-grants-2013_07
Patent number
US08481524B2

Reaction notes

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