Sodium Bicarbonate → ethyl 2-(6-amino-5-(1-(2,3-difluorophenyl)-1H-tetrazol-5-yl)pyridin-3-yl)-4,5,7,8-tetrahydrothieno[3,2-d]azepine-6-carboxylate

HRID 254008Notes

Reaction equation

HRID 254008 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[N:9]1[C:13]([C:14]2[C:15]([NH2:29])=[N:16][CH:17]=[C:18](B3OC(C)(C)C(C)(C)O3)[CH:19]=2)=[N:12][N:11]=[N:10]1.Br[C:31]1[S:40][C:39]2[CH2:38][CH2:37][N:36]([C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:35][CH2:34][C:33]=2[CH:32]=1.C([O-])(O)=O.[Na+]>CN(C)C=O.C(OCC)(=O)C.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]>[NH2:29][C:15]1[N:16]=[CH:17][C:18]([C:31]2[S:40][C:39]3[CH2:38][CH2:37][N:36]([C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:35][CH2:34][C:33]=3[CH:32]=2)=[CH:19][C:14]=1[C:13]1[N:9]([C:3]2[CH:4]=[CH:5][CH:6]=[C:7]([F:8])[C:2]=2[F:1])[N:10]=[N:11][N:12]=1

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 57354995Ethyl 2-bromo-4,5,7,8-tetrahydro-6H-thieno[2,3-d]azepine-6-carboxylateHCID 581794573-(1-(2,3-difluorophenyl)-1H-tetrazol-5-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine

Product 1

HCID 58179782ethyl 2-(6-amino-5-(1-(2,3-difluorophenyl)-1H-tetrazol-5-yl)pyridin-3-yl)-4,5,7,8-tetrahydrothieno[3,2-d]azepine-6-carboxylate

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

A mixture of 3-(1-(2,3-difluorophenyl)-1H-tetrazol-5-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (2.50 g, 6.3 mmol), ethyl 2-bromo-4,5,7,8-tetrahydrothieno[3,2-d]azepine-6-carboxylate (1.91 g, 06.3 mmol), and NaHCO3 (15.6 mL, saturated solution in H2O) in N,N-dimethylformamide (83 mL) was degassed with a nitrogen stream for 20 min. To this mixture was added [1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloride (460 mg, 0.6 mmol) and the reaction was stirred in a microwave for 10 min at 120° C. The resulting crude mixture was diluted with ethyl acetate (300 mL) and filtered. The filtrate washed with H2O (2×150 mL) and brine (1×150 mL), concentrated under reduced pressure, and purified via silica gel chromatography to provide ethyl 2-(6-amino-5-(1-(2,3-difluorophenyl)-1H-tetrazol-5-yl)pyridin-3-yl)-4,5,7,8-tetrahydrothieno[3,2-d]azepine-6-carboxylate.

Workup

  1. customwas degassed with a nitrogen stream for 20 min
  2. filtrationfiltered
  3. washThe filtrate washed with H2O (2×150 mL) and brine (1×150 mL)
  4. concentrationconcentrated under reduced pressure
  5. custompurified via silica gel chromatography

Sources & evidence

ORD record
ord-ee84704b36944975ba9f70aad9fcc337
Source dataset
uspto-grants-2011_01
Patent number
US07872031B2

Reaction notes

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