Diisopropylethylamine → HCID 67209217, compound

HRID 402494Notes

Reaction equation

HRID 402494 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[CH:9]([NH2:13])[CH2:8][CH2:7]2.[CH:14]1([C:17]2[C:25]3[C:20](=[N:21][C:22]([O:27][CH2:28][C:29](O)=[O:30])=[CH:23][C:24]=3[CH3:26])[N:19]([CH3:32])[N:18]=2)[CH2:16][CH2:15]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>CN(C=O)C.CCOC(C)=O>[CH:14]1([C:17]2[C:25]3[C:20](=[N:21][C:22]([O:27][CH2:28][C:29]([NH:13][CH:9]4[C:10]5[C:6](=[CH:5][C:4]([O:3][CH3:2])=[CH:12][CH:11]=5)[CH2:7][CH2:8]4)=[O:30])=[CH:23][C:24]=3[CH3:26])[N:19]([CH3:32])[N:18]=2)[CH2:15][CH2:16]1

Participants

7

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 53415081HCID 53415081, compoundHCID 67209204HCID 67209204, compound

Product 1

HCID 67209217HCID 67209217, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To the solution of 5-methoxy-indan-1-ylamine hydrochloride (92 mg, 0.46 mmol) and (3-cyclopropyl-1,4-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yloxy)-acetic acid (building block A7, 120 mg, 0.46 mmol) in DMF (6 ml) were added DIPEA (0.24 ml, 1.38 mmol) and HATU (210 mg, 0.55 mmol) and the reaction was stirred at it for 30 min. The mixture was diluted with EtOAc, washed with aqueous bicarbonate solution and brine, dried over sodium sulfate, and the solvents were evaporated under reduced pressure. Purification by preparative HPLC (Gilson GX-281, Waters Sunfire C18, 5 μm, 30×100 mm with guard column 19×10 mm, solvent A: water with 0.1% TFA, solvent B: acetonitrile, gradient 40-60% B in 15 min, flow reate 50 ml/min) gave the title compound as colorless solid (140 mg, 75%). [1H-NMR (DMSO-d6, 600 MHz) δ 8.40 (d, 1H), 7.02 (d, 1H), 6.81 (s, 1H), 6.68 (d, 1H), 6.48 (s, 1H), 5.26 (dd, 1H), 4.80 (s, 2H), 3.76 (s, 3H), 3.71 (s, 3H), 2.91-2.88 (m, 1H), 2.78-2.73 (m, 1H), 2.66 (s, 3H), 2.38-2.33 (m, 1H), 2.28-2.24 (m, 1H), 1.89-1.82 (m, 1H), 0.92-0.85 (m, 4H); LCMS RtH=3.095 min; [M+H]+=407.2]

Workup

  1. washwashed with aqueous bicarbonate solution and brine
  2. dry with materialdried over sodium sulfate
  3. customthe solvents were evaporated under reduced pressure
  4. customPurification by preparative HPLC (Gilson GX-281, Waters Sunfire C18, 5 μm, 30×100 mm with guard column 19×10 mm, solvent A: water with 0.1% TFA, solvent B: acetonitrile, gradient 40-60% B in 15 min, flow reate 50 ml/min)

Sources & evidence

ORD record
ord-7bde71399bad4e5282edd44e26a14fac
Source dataset
uspto-grants-2014_06
Patent number
US08742106B2

Reaction notes

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