Diisopropylethylamine → HCID 71217520, compound

HRID 1485215Notes

Reaction equation

HRID 1485215 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([NH:18][C:19]3[N:24]=[C:23]([CH2:25][CH2:26][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=4[CH2:33][C:34]([O-:36])=O)[C:22]([C:37]([F:40])([F:39])[F:38])=[CH:21][N:20]=3)[CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li+].C[N:43](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(=O)([O-])[O-].[NH4+].[NH4+].CCN(C(C)C)C(C)C.C(=O)(O)[O-].[Na+]>CN(C=O)C.O>[NH2:43][C:34](=[O:36])[CH2:33][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=1[CH2:26][CH2:25][C:23]1[C:22]([C:37]([F:39])([F:38])[F:40])=[CH:21][N:20]=[C:19]([NH:18][C:13]2[CH:14]=[C:15]3[C:10](=[CH:11][CH:12]=2)[CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7])[CH2:17][CH2:16]3)[N:24]=1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 517111Ammonium CarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68282987HCID 68282987, compound

Product 1

HCID 71217520HCID 71217520, compoundYield 67.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Lithium 2-(2-(2-(2-((2-(tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetate (I81) (205 mg, 0.37 mmol) was dissolved in DMF (3 mL) and HATU (154 mg, 0.41 mmol) was added. After stirring for 3 minutes, ammonium carbonate (212 mg, 2.20 mmol) and DIPEA (0.26 mL, 1.5 mmol) were added and the mixture was stirred at room temperature for 18 hours. The resulting mixture was added to water (50 mL) and saturated sodium bicarbonate (10 mL) then extracted with ethyl acetate (3×50 mL). The organic extracts were washed with brine (2×50 mL), dried (sodium sulphate) and evaporated to dryness. The residue was chromatographed (12 g silica cartridge, 0-100% ethyl acetate/petroleum benzine 40-60° C.) and the product triturated with diethyl ether to give the title compound (I82) (138 mg, 67%) as an off-white foam; 1H NMR (400 MHz, CDCl3) δ 8.53 (s, 1H), 7.57 (s, 1H), 7.43 (d, J=8.9 Hz, 2H), 7.29-7.26 (m, overlaps with CHCl3), 7.10 (d, J=8.4 Hz, 1H), 5.36 (d, J=14.4 Hz, 2H), 4.55 (s, 2H), 3.73 (s, 2H), 3.65 (s, 2H), 3.15-3.04 (m, 4H), 2.85 (t, J=5.8 Hz, 2H), 1.50 (s, 9H). LCMS Method C: rt 6.36 min; m/z 556.1 [M+H]+, 500.0 [M-tBu+2H]+, 456.1 [M-Boc+2H]+; m/z 554.2 [M−H]−.

Workup

  1. stirringthe mixture was stirred at room temperature for 18 hours
  2. extractionthen extracted with ethyl acetate (3×50 mL)
  3. washThe organic extracts were washed with brine (2×50 mL)
  4. dry with materialdried (sodium sulphate)
  5. customevaporated to dryness
  6. customThe residue was chromatographed (12 g silica cartridge, 0-100% ethyl acetate/petroleum benzine 40-60° C.)
  7. customthe product triturated with diethyl ether

Sources & evidence

ORD record
ord-269cf99c0da0479e892993bc866594f6
Source dataset
uspto-grants-2016_08
Patent number
US09421205B2

Reaction notes

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