Diisopropylethylamine → HCID 178523811, compound

HRID 1678687Notes

Reaction equation

HRID 1678687 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]([CH:17]([CH:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]3)[C:18](O)=[O:19])=[C:15]3[C:10]([CH2:11][CH2:12][CH2:13][CH2:14]3)=[N:9]2)=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:60][C@H:61]1[CH2:66][CH2:65][C@H:64]([OH:67])[CH2:63][CH2:62]1>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]([CH:17]([CH:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]3)[C:18]([NH:60][C@H:61]3[CH2:66][CH2:65][C@H:64]([OH:67])[CH2:63][CH2:62]3)=[O:19])=[C:15]3[C:10]([CH2:11][CH2:12][CH2:13][CH2:14]3)=[N:9]2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67131112[2-(4-Chloro-phenyl)-4,5,6,7-tetrahydro-2H-indazol-3-yl]-cyclohexyl-acetic acidHCID 178511715HCID 178511715, compound

Product 1

HCID 178523811HCID 178523811, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of [2-(4-chloro-phenyl)-4,5,6,7-tetrahydro-2H-indazol-3-yl]-cyclohexyl-acetic acid (200 mg, 0.54 mmol; example 5.1) in dry DMF (4 mL) was added dry DIPEA (3.2 mmol) followed by HATU (1.6 mmol) at 0° C. Then the reaction mixture was allowed to warm to rt and stirred for 45 min at that temperature. TLC shows total consumption of acid and formation of a new spot. (trans)-4-Amino-cyclohexanol (0.64 mmol) was added to this reaction mixture at 0° C. Then the cooling bath was removed and the reaction mixture was stirred at room temperature for 16 h. TLC shows total consumption of [2-(4-chloro-phenyl)-4,5,6,7-tetrahydro-2H-indazol-3-yl]-cyclohexyl-acetic acid and DMF was removed in vacuo at 60° C. It was then diluted with H2O (5 ml). Aqueous layer was extracted with EtOAc (5×5 mL) and combined organic layers were washed with brine (50 ml), dried over Na2SO4 and concentrated in vacuo. Crude product was subjected to column chromatography [SiO2 (230-400 mesh), EtOAc:Hexane 10:90] to give the title compound (40 mg, 24%) as off-white solid. MS: m/e=470.0 [M+H+].

Workup

  1. customconsumption of acid and formation of a new spot
  2. customThen the cooling bath was removed
  3. stirringthe reaction mixture was stirred at room temperature for 16 h
  4. customconsumption of [2-(4-chloro-phenyl)-4,5,6,7-tetrahydro-2H-indazol-3-yl]-cyclohexyl-acetic acid and DMF
  5. customwas removed in vacuo at 60° C
  6. additionIt was then diluted with H2O (5 ml)
  7. extractionAqueous layer was extracted with EtOAc (5×5 mL)
  8. washwere washed with brine (50 ml)
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0006a5f021f24bfb8d0c27a5a5a6e5aa
Source dataset
uspto-grants-2011_08
Patent number
US08008505B2

Reaction notes

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