Diisopropylethylamine → HCID 70817047, compound

HRID 402493Notes

Reaction equation

HRID 402493 reaction equation
Cl.[CH3:2][C:3]1[CH:11]=[CH:10][C:9]2[C@@H:8]([NH2:12])[CH2:7][CH2:6][C:5]=2[N:4]=1.[CH:13]1([C:16]2[C:24]3[C:19](=[N:20][C:21]([O:28][CH2:29][C:30](O)=[O:31])=[CH:22][C:23]=3[CH:25]([F:27])[F:26])[N:18]([CH3:33])[N:17]=2)[CH2:15][CH2:14]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:13]1([C:16]2[C:24]3[C:19](=[N:20][C:21]([O:28][CH2:29][C:30]([NH:12][C@@H:8]4[C:9]5[C:5](=[N:4][C:3]([CH3:2])=[CH:11][CH:10]=5)[CH2:6][CH2:7]4)=[O:31])=[CH:22][C:23]=3[CH:25]([F:26])[F:27])[N:18]([CH3:33])[N:17]=2)[CH2:14][CH2:15]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 67209178HCID 67209178, compoundHCID 88995458HCID 88995458, compound

Product 1

HCID 70817047HCID 70817047, compoundYield 72.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To the solution of (S)-2-methyl-6,7-dihydro-5H-[1]pyrindin-5-ylamine hydrochloride (75 mg, 0.41 mmol) and (3-cyclopropyl-4-difluoromethyl-1-methyl-1H-pyrazolo[3,4-b]pyridin-6-yloxy)-acetic acid (building block A2, 110 mg, 0.37 mmol) in DMF (6 ml) were added DIPEA (0.26 ml, 1.48 mmol) and HATU (169 mg, 0.44 mmol) and the reaction was stirred at it for 3 h. 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 10-30% B in 16 min, flow rate 50 ml/min) gave the title compound as off-white solid (115 mg, 72%). [1H-NMR (DMSO-d6, 600 MHz) δ 8.61 (d, 1H), 7.47 (t, 1H), 7.36 (d, 1H), 6.99 (d, 1H), 6.93 (s, 1H), 5.32 (dd, 1H), 4.89 (s, 2H), 3.81 (s, 3H), 3.34 (s, 3H), 2.93-2.89 (m, 1H), 2.86-2.80 (m, 1H), 2.41 (s, 3H), 2.41-2.36 (m, 1H), 2.24-2.19 (m, 1H), 1.92-1.86 (m, 1H), 0.94-0.87 (m, 4H); LCMS RtI=3.032 min; [M+H]+=428.2]

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 10-30% B in 16 min, flow rate 50 ml/min)

Sources & evidence

ORD record
ord-d3c4462b4b5b4d86985b4e8b5d4f2ecf
Source dataset
uspto-grants-2014_06
Patent number
US08742106B2

Reaction notes

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