Benzylamine → HCID 178517969, compound

HRID 1641308Notes

Reaction equation

HRID 1641308 reaction equation
Br[C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]2[CH2:33][CH2:32][C:12]3([N:16]([C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=4)[C:15](=[O:24])[N:14]=[C:13]3[NH:25][CH:26]3[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]3)[CH2:11][CH2:10]2)=[CH:4][CH:3]=1.CC(C)([O-])C.[Na+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH2:86]([NH2:93])[C:87]1[CH:92]=[CH:91][CH:90]=[CH:89][CH:88]=1.FC(F)(F)C([O-])=O.FC(F)(F)C([O-])=O.C(NC1[NH+]=CC(C[NH+]2CCC3(N(C4C=CC=C(F)C=4)C(=O)N=C3NC3CCCCC3)CC2)=CC=1)C1C=CC=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[CH2:86]([NH:93][C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]2[CH2:33][CH2:32][C:12]3([N:16]([C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=4)[C:15](=[O:24])[N:14]=[C:13]3[NH:25][CH:26]3[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]3)[CH2:11][CH2:10]2)=[CH:4][CH:3]=1)[C:87]1[CH:92]=[CH:91][CH:90]=[CH:89][CH:88]=1

Participants

8

Reactant 5

HCID 7504BenzylamineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 178517965HCID 178517965, compoundHCID 178525682HCID 178525682, compound

Product 1

HCID 178517969HCID 178517969, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a 600 μL dried degassed toluene suspension of 27 mg (0.052 mmol) 8-[(6-bromopyridin-3-yl)methyl]-4-(cyclohexylamino)-1-(3-fluorophenyl)-1,3,8-triazaspiro[4.5]dec-3-en-2-one (8-1, prepared in the same manner as Intermediate 5-3), 9 mg (0.094 mmol) sodium t-butoxide, 2 mg (0.003 mmol) racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP), and 2 mg (0.003 mmol) tris(dibenzylideneacetone)dipalladium (0) was added 29 μL (0.262 mmol) benzylamine. The reaction vessel was capped and warmed to 110° C. overnight. The clear toluene layer was decanted and the residue extracted (2× hot toluene). The combined organic extracts were concentrated to dryness in vacuo, the residue dissolved in 900 μL DMF and purified by preparative HPLC (5→95% CH3CN/H2O over 30 m, 0.05% added TFA, C18 PRO YMC 20×150 mm) to afford, after lyophilization, 8-{[6-(benzylamino)pyridinium-3-yl]methyl}-4-(cyclohexylamino)-1-(3-fluorophenyl)-2-oxo-1,3-diaza-8-azoniaspiro[4.5]dec-3-ene bis(trifluoroacetate) as a white fluffy solid. 1H NMR (CD3OD with K2CO3, 400 MHz): δ 7.70 (s, 1H), 7.34 (m, 5H), 7.23 (m, 2H), 7.08 (m, 3H), 6.47 (d, J=8.60 Hz, 1H), 4.49 (s, 2H), 3.77 (m, 1H), 3.28 (s, 2H), 2.68 (m, 2H), 2.12 (m, 4H), 2.00 (m, 4H), 1.80 (m, 2H), 1.68 (m, 1H), 1.33 (m, 5H). High resolution mass spec (FT/ICR): calc M+H=541.3086. found 541.3103

Workup

  1. customTo a 600 μL dried
  2. customdegassed
  3. customThe reaction vessel was capped
  4. customThe clear toluene layer was decanted
  5. extractionthe residue extracted (2× hot toluene)
  6. concentrationThe combined organic extracts were concentrated to dryness in vacuo
  7. dissolutionthe residue dissolved in 900 μL DMF
  8. custompurified by preparative HPLC (5→95% CH3CN/H2O over 30 m, 0.05%
  9. additionadded TFA
  10. customC18 PRO YMC 20×150 mm) to afford

Sources & evidence

ORD record
ord-db81652df0bf4643ac46b4a5a0e2c832
Source dataset
uspto-grants-2012_02
Patent number
US08114887B2

Reaction notes

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