Triethylamine → HCID 178471810, compound

HRID 1099470Notes

Reaction equation

HRID 1099470 reaction equation
[CH:1]1([CH:7]([N:11]2[C:15]3[CH:16]=[CH:17][C:18]([F:20])=[CH:19][C:14]=3[N:13]=[C:12]2[C@H:21]([O:28][CH3:29])[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:8]([OH:10])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[CH2:62]([O:64][C:65](=[O:74])[CH2:66][C@H:67]1[CH2:72][CH2:71][C@H:70]([NH2:73])[CH2:69][CH2:68]1)[CH3:63]>CN(C=O)C>[CH2:62]([O:64][C:65](=[O:74])[CH2:66][C@H:67]1[CH2:68][CH2:69][C@H:70]([NH:73][C:8](=[O:10])[CH:7]([CH:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)[N:11]2[C:15]3[CH:16]=[CH:17][C:18]([F:20])=[CH:19][C:14]=3[N:13]=[C:12]2[C@H:21]([O:28][CH3:29])[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH2:71][CH2:72]1)[CH3:63]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66810397Cyclohexyl-[5-fluoro-2-((R)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-acetic acidHCID 178471807HCID 178471807, compound

Product 1

HCID 178471810HCID 178471810, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of cyclohexyl-[5-fluoro-2-((R)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-acetic acid (350 mg, 0.88 mmol, 1.0 equiv) in DMF (5 mL) was added triethylamine (179 mg, 240 μL, 1.77 mmol, 2.0 equiv) and HATU (403 mg, 1.06 mmol, 1.2 equiv) and the mixture stirred at 40° C. After 15 min, trans-(4-amino-cyclohexyl)-acetic acid ethyl ester hydrochloride (235 mg, 1.06 mmol, 1.2 equiv; [CAS RN 76308-26-4]) was added and stirring continued at 50° C. for 2 h. The solution was concentrated by evaporation under reduced pressure, the pH adjusted to 9 by addition of a solution of 1 M NaHCO3 and the aqueous layer extracted with dichloromethane. The combined organic phases were dried over MgSO4 and concentrated by evaporation under reduced pressure. The crude material was used in the consecutive step without further purification. MS (ISP): 564.7 [M+H]+.

Workup

  1. stirringstirring
  2. waitcontinued at 50° C. for 2 h
  3. concentrationThe solution was concentrated by evaporation under reduced pressure
  4. additionthe pH adjusted to 9 by addition of a solution of 1 M NaHCO3
  5. extractionthe aqueous layer extracted with dichloromethane
  6. dry with materialThe combined organic phases were dried over MgSO4
  7. concentrationconcentrated by evaporation under reduced pressure
  8. customThe crude material was used in the consecutive step without further purification

Sources & evidence

ORD record
ord-747f2af6408c428893586a4a20524c1c
Source dataset
uspto-grants-2012_03
Patent number
US08143422B2

Reaction notes

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