Triethylamine → HCID 178482086, compound

HRID 2092391Notes

Reaction equation

HRID 2092391 reaction equation
[C:1]([NH:8][C@H:9]1[CH2:14][CH2:13][C@H:12]([C:15]([OH:17])=O)[CH2:11][CH2:10]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[Br:18][C:19]1[CH:26]=[CH:25][C:22]([NH:23][CH3:24])=[CH:21][CH:20]=1.CCN(CC)CC.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CC(OC)(C)C>[C:4]([O:3][C:1](=[O:2])[NH:8][C@H:9]1[CH2:10][CH2:11][C@H:12]([C:15](=[O:17])[N:23]([C:22]2[CH:25]=[CH:26][C:19]([Br:18])=[CH:20][CH:21]=2)[CH3:24])[CH2:13][CH2:14]1)([CH3:5])([CH3:6])[CH3:7]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 2757052Benzenamine, 4-bromo-N-methyl-HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 178453972HCID 178453972, compound

Product 1

HCID 178482086HCID 178482086, compoundYield 39%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of trans-4-(Boc-amino)cyclohexanecarboxylic acid (148 mg, 0.608 mmol) in DMF were successively added 4-bromo-N-methylaniline (0.084 ml, 0.669 mmol), Et3N (0.170 ml, 1.217 mmol) and HATU (278 mg, 0.730 mmol) at RT. The reaction mixture was heated at 80° C. for 6 h then additional HATU (278 mg, 0.730 mmol) was added and the mixture was further stirred at 80° C. for 14 h. The reaction mixture was cooled to RT, diluted with TBME and washed successively with HCl 2M in water and Na2CO3 2M in water. The organic phase was dried over Na2SO4, filtered and evaporated to dryness. The resulting crude material was purified by reverse phase prep-HPLC (gradient elution, H2O containing 0.1% TFA/MeCN 8:8→2:8) to yield the title compound (97 mg, 0.236 mmol, 39%) as a brownish solid. HPLC: AtRet=2.38 min; LC-MS: m/z 411.4 [M+H]+; 1H NMR (400 MHz, DMSO-d6): 0.73-0.99 (m, 2H), 1.35 (s, 9H), 1.32-1.45 (m, 3H), 1.55-1.76 (m, 4H), 1.86-2.15 (m, 1H), 3.11 (br. s., 3H), 6.56 (br. s., 1H), 7.27-7.35 (m, 2H), 7.61-7.69 (m, 2H).

Workup

  1. customat RT
  2. temperatureThe reaction mixture was cooled to RT
  3. washwashed successively with HCl 2M in water and Na2CO3 2M in water
  4. dry with materialThe organic phase was dried over Na2SO4
  5. filtrationfiltered
  6. customevaporated to dryness
  7. customThe resulting crude material was purified by reverse phase prep-HPLC (gradient elution, H2O containing 0.1% TFA/MeCN 8:8→2:8)

Sources & evidence

ORD record
ord-1c963bc0f77a4072861699cc7f90ca7b
Source dataset
uspto-grants-2013_05
Patent number
US08440693B2

Reaction notes

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