Diisopropylethylamine → HCID 178521900, compound

HRID 1678683Notes

Reaction equation

HRID 1678683 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.[NH:60]1[C:64]([C:65]2[CH:70]=[CH:69][C:68]([NH2:71])=[CH:67][CH:66]=2)=[N:63][N:62]=[N:61]1>CN(C=O)C>[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]([NH:71][C:68]3[CH:69]=[CH:70][C:65]([C:64]4[NH:60][N:61]=[N:62][N:63]=4)=[CH:66][CH:67]=3)=[O:19])=[C:15]3[C:10]([CH2:11][CH2:12][CH2:13][CH2:14]3)=[N:9]2)=[CH:4][CH:3]=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 178507471HCID 178507471, compound

Product 1

HCID 178521900HCID 178521900, compound

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 (250 mg, 0.67 mmol; example 5.1) in dry DMF (12 mL) was added dry DIPEA (0.375 ml, 2.32 mmol) followed by HATU (510 mg, 1.34 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. 4-(1H-Tetrazol-5-yl)-phenylamine (162.5 mg, 1.02 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 50° C. It was then diluted with H2O (15 ml). Aqueous layer was extracted with EtOAc (4×20 mL) and combined organic layers were washed with brine (20 ml), dried over Na2SO4 and concentrated in vacuo. Crude product (355.0 mg) was subjected to column chromatography [SiO2 (230-400 mesh), McOH:DCM 5:95] to give the title compound as brownish sticky solid. Yield (170 mg, 52%). MS: m/e=516.0 [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 50° C
  6. additionIt was then diluted with H2O (15 ml)
  7. extractionAqueous layer was extracted with EtOAc (4×20 mL)
  8. washwere washed with brine (20 ml)
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0f469ac75b714675a8ab7b533581fb7e
Source dataset
uspto-grants-2011_08
Patent number
US08008505B2

Reaction notes

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