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Sodium Bicarbonate → HCID 58179868, compound

HRID 1518562
Notes
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Reaction equation

HRID 1518562 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH2:10][CH2:11][CH2:12][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:14][CH:15]=2)O1.C([O-])(O)=O.[Na+].Br[C:30]1[CH:31]=[C:32]([C:37]2[N:41]([C:42]3[CH:47]=[CH:46][CH:45]=[C:44]([F:48])[C:43]=3[F:49])[N:40]=[N:39][N:38]=2)[C:33]([NH2:36])=[N:34][CH:35]=1>COCCOC.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]>[NH2:36][C:33]1[N:34]=[CH:35][C:30]([C:9]2[CH2:10][CH2:11][CH2:12][N:13]([C:16]([O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:17])[CH2:14][CH:15]=2)=[CH:31][C:32]=1[C:37]1[N:41]([C:42]2[CH:47]=[CH:46][CH:45]=[C:44]([F:48])[C:43]=2[F:49])[N:40]=[N:39][N:38]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 247624635-bromo-3-(1-(2,3-difluorophenyl)-1H-tetrazol-5-yl)pyridin-2-amineHCID 581796955-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3,4,7-tetrahydroazepine-1-carboxylic acid tert-butyl ester

Product 1

HCID 58179868HCID 58179868, compoundYield 58.5%

Reagents, catalysts & solvents 2

HCID 44119782
Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)
Catalyst
2×
HCID 80711,2-DimethoxyethaneSolvent

Procedure

(Z)-tert-Butyl 3,4-dihydro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-azepine-1(7H)-carboxylate (510 mg, 1.44 mmol, 1.1 eq.) was dissolved in DME (14 mL) and degassed with nitrogen for 15 minutes. NaHCO3 (1.2 M solution, 3.25 mL, 3.9 mmol, 3 eq.) and 5-bromo-3-(1-(2,3-difluorophenyl)-1H-tetrazol-5-yl)pyridin-2-amine (420 mg, 1.3 mmol, 1 eq.) were added and the mixture degassed with nitrogen for an additional 30 minutes. PdCl2(dppf)2 (95 mg, 0.13 mmol, 0.1 eq.) was added and the mixture degassed with nitrogen for an additional 15 minutes. The reaction was microwaved in a sealed tube for 20 min at 90° C. To drive the reaction to completion, additional PdCl2(dppf)2 (95 mg, 0.13 mmol, 0.1 eq.) was added under an atmosphere of nitrogen and the reaction microwaved for an additional 20 min at 90° C. The mixture was concentrated, NaHCO3 was added, and the product was extracted with ethyl acetate. The organics were filtered through floricil and purified by silica gel chromatography (EtOAc/hexanes) to provide (E)-tert-butyl 5-(6-amino-5-(1-(2,3-difluorophenyl)-1H-tetrazol-5-yl)pyridin-3-yl)-3,4-dihydro-2H-azepine-1(7H)-carboxylate (360 mg, 0.76 mmol, 53% yield); 1H NMR (300 MHz, CDCl3): 8.2 (m, 1H); 7.5 (m, 1H); 7.45-7.3 (m, 2H); 7.02 (s, 1H); 6.4 (br s, 2H); 5.6 (m, 1H); 3.8 (m, 2H); 3.55 (m, 2H); 2.2 (m, 2H); 1.7 (m, 2H) 1.45 (s, 9H).

Workup

  1. customdegassed with nitrogen for 15 minutes
  2. customthe mixture degassed with nitrogen for an additional 30 minutes
  3. customthe mixture degassed with nitrogen for an additional 15 minutes
  4. customThe reaction was microwaved in a sealed tube for 20 min at 90° C
  5. additionwas added under an atmosphere of nitrogen
  6. customthe reaction microwaved for an additional 20 min at 90° C
  7. concentrationThe mixture was concentrated
  8. additionNaHCO3 was added
  9. extractionthe product was extracted with ethyl acetate
  10. filtrationThe organics were filtered through floricil
  11. custompurified by silica gel chromatography (EtOAc/hexanes)

Sources & evidence

ORD record
ord-c8bfd342730545c98da69e90cc70917a
Source dataset
uspto-grants-2012_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08232406B2

Reaction notes

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