Triphenylphosphine → 3-(3-(4-(3-Ethynyl-benzyloxy)-benzyl)-isoxazol-5-yl)-pyridin-2,6-diamine

HRID 78262Notes

Reaction equation

HRID 78262 reaction equation
[NH2:1][C:2]1[C:7]([C:8]2[O:12][N:11]=[C:10]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=3)[CH:9]=2)=[CH:6][CH:5]=[C:4]([NH2:21])[N:3]=1.[C:22]([C:24]1[CH:25]=[C:26]([CH2:30]O)[CH:27]=[CH:28][CH:29]=1)#[CH:23].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[C:22]([C:24]1[CH:25]=[C:26]([CH:27]=[CH:28][CH:29]=1)[CH2:30][O:20][C:17]1[CH:18]=[CH:19][C:14]([CH2:13][C:10]2[CH:9]=[C:8]([C:7]3[C:2]([NH2:1])=[N:3][C:4]([NH2:21])=[CH:5][CH:6]=3)[O:12][N:11]=2)=[CH:15][CH:16]=1)#[CH:23]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 154687703-EthynylbenzenemethanolHCID 592553274-(5-(2,6-Diamino-pyridine-3-yl)-isoxazol-3-ylmethyl)phenol

Product 1

HCID 592551973-(3-(4-(3-Ethynyl-benzyloxy)-benzyl)-isoxazol-5-yl)-pyridin-2,6-diamineYield 52.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a tetrahydrofuran (10 mL) solution of 4-(5-(2,6-diamino-pyridin-3-yl)-isoxazol-3-ylmethyl)-phenol (150 mg, 0.53 mmol) described in Manufacturing Example 18-1-1, (3-ethynyl-phenyl)-methanol (91 mg, 0.69 mmol) described in Manufacturing Example 214-1-2, and triphenylphosphine (180 mg, 0.69 mmol) was added diethyl azodicarboxylate (300 mg, 0.69 mmol, 40% toluene solution), which was stirred for 30 minutes at room temperature. NH silica gel was added to the reaction solution, and the solvent was evaporated under a reduced pressure. The crude product that had adsorbed to the NH silica gel was purified by NH silica gel column chromatography (heptane:ethyl acetate=2:1, then 1:1, then ethyl acetate) to obtain the title compound (110 mg, 51%).

Workup

  1. additionNH silica gel was added to the reaction solution
  2. customthe solvent was evaporated under a reduced pressure
  3. customwas purified by NH silica gel column chromatography (heptane

Sources & evidence

ORD record
ord-5e0c84c3f98249d7942828289dfb2804
Source dataset
uspto-grants-2014_09
Patent number
US08841327B2

Reaction notes

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