Diisopropylethylamine → HCID 90077458, compound

HRID 1050274Notes

Reaction equation

HRID 1050274 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[NH:18][C:17]([O:19][C@H:20]3[CH2:25][O:24][C@H:23]([CH2:26][OH:27])[C@@H:22]([OH:28])[CH2:21]3)=[N:16][C:5]2=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14]#[CH:15])=[CH:10][CH:9]=1.Br[C:30]1[N:31]=[N:32][N:33]([CH3:35])[N:34]=1.C(N(C(C)C)CC)(C)C>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[Cl:1][C:2]1[CH:3]=[C:4]2[NH:18][C:17]([O:19][C@H:20]3[CH2:25][O:24][C@H:23]([CH2:26][OH:27])[C@@H:22]([OH:28])[CH2:21]3)=[N:16][C:5]2=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14]#[C:15][C:30]2[N:31]=[N:32][N:33]([CH3:35])[N:34]=2)=[CH:10][CH:9]=1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 217664245-Bromo-2-methyl-1H-tetrazoleHCID 90077264HCID 90077264, compound

Product 1

HCID 90077458HCID 90077458, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of (2R,3 S,5R)-5-((6-chloro-5-(4-ethynylphenyl)-1H-imidazo[4,5-b]pyridin-2-yl)-oxy)-2-(hydroxymethyl)tetrahydro-2H-pyran-3-ol (60 mg, 0.150 mmol), Pd(Ph3P)4(17.34 mg, 0.015 mmol), copper(I) iodide (2.85 mg, 0.015 mmol), 5-bromo-2-methyl-2H-tetrazole (48.9 mg, 0.300 mmol) and diisopropylethylamine (0.210 ml, 0.450 mmol) in dioxane (2 ml) was charged in a reaction tube. The tube was sealed and N2 was bubbled through for 5 min. The reaction was heated at 80 C for 18 h, and then concentrated. The resulting residue was purified on reverse phase HPLC eluting with 10-70% CH3CN/H2O with TFA as an additive to give the title compound. LC-MS: m/e: 481.97.53 (M+H)+ (Rt 1.70/4 min); 1H NMR δ (ppm) (CD3OD): 7.84-7.75 (m, 4H), 5.11 (septet, 1H, J=5 Hz)), 4.38-4.31 (m, 1H), 4.24 (s, 3H), 3.89 (dd, 1H, J=12, 2 Hz), 3.69-3.59 (m, 2H), 3.37 (t, 1H, J=11 Hz), 3.20-3.15 (m, 1H), 2.79-2.72 (m, 1H), 1.70 (dd, 1H, J=23, 12 Hz),

Workup

  1. additionwas charged in a reaction tube
  2. customThe tube was sealed
  3. customN2 was bubbled through for 5 min
  4. temperatureThe reaction was heated at 80 C for 18 h
  5. concentrationconcentrated
  6. customThe resulting residue was purified on reverse phase HPLC
  7. washeluting with 10-70% CH3CN/H2O with TFA as an additive

Sources & evidence

ORD record
ord-672cc64889a742e3bfc28b2c74a80e83
Source dataset
uspto-grants-2016_07
Patent number
US09382243B2

Reaction notes

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