Triphenylphosphine → HCID 11508927, compound

HRID 1864615Notes

Reaction equation

HRID 1864615 reaction equation
[CH3:1][C:2]1[S:6][C:5]([C:7]2[CH:15]=[C:14]3[C:10]([C:11]([C:16]([OH:18])=[O:17])=[N:12][NH:13]3)=[CH:9][CH:8]=2)=[N:4][CH:3]=1.[N:19]12[CH2:26][CH2:25][CH:22]([CH2:23][CH2:24]1)[C@@H:21](O)[CH2:20]2.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1>[CH3:1][C:2]1[S:6][C:5]([C:7]2[CH:15]=[C:14]3[C:10]([C:11]([C:16]([O:18][C@H:21]4[CH:22]5[CH2:25][CH2:26][N:19]([CH2:24][CH2:23]5)[CH2:20]4)=[O:17])=[N:12][NH:13]3)=[CH:9][CH:8]=2)=[N:4][CH:3]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 914043-Quinuclidinol, (-)-HCID 66932538HCID 66932538, compound

Product 1

HCID 11508927HCID 11508927, compoundYield 1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 6-(5-methyl-1,3-thiazol-2-yl)-1H-indazole-3-carboxylic acid (0.50 mmol), (3R)-quinuclidin-3-ol (0.57 mmol), and triphenylphosphine (0.57 mmol) in tetrahydrofuran (5 mL) at 0° C. was added a solution of diisopropyl azodicarboxylate (0.57 mmol) in tetrahydrofuran (1 mL). The mixture was allowed to warm to rt over 2 hours and was maintained for 16 h. The mixture was loaded on a SCX column (5 g) and was washed with methanol. Product was eluted with methanol/dimethylethylamine (9/1) and concentrated. The residue was purified by preparative HPLC to produce the desired product in 1% yield. 1H NMR (CD3OD) δ 8.65 (s, 1 H), 8.51 (s, 1 H), 8.04 (d, J=6.0, 1H), 7.74 (d, J=6.0, 1 H), 7.55 (s, 1 H), 5.45 (m, 1 H), 3.81 (m, 1 H), 3.45-3.20 (m, 5H), 2.55 (s, 3 H), 2.55 (m, 1 H), 2.36 (m, 1 H), 2.21-1.93 (m, 3 H); LC/MS (EI) tR 4.7 min, m/z 369 (M++1).

Workup

  1. temperaturewas maintained for 16 h
  2. washwas washed with methanol
  3. washProduct was eluted with methanol/dimethylethylamine (9/1)
  4. concentrationconcentrated
  5. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-3e97ce27f4ec444fa54a5348a12a9366
Source dataset
uspto-grants-2009_12
Patent number
US07625924B2

Reaction notes

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