1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → (R)-1-(4-(8-(4-methoxyphenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino)-1H-pyrazol-1-yl)propan-2-ol

HRID 57774Notes

Reaction equation

HRID 57774 reaction equation
I[C:2]1[N:18]=[C:5]2[C:6]([C:10]3[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=3)=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.[NH2:19][C:20]1[CH:21]=[N:22][N:23]([CH2:25][C@H:26]([OH:28])[CH3:27])[CH:24]=1.CC(C)([O-])C.[Na+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:17][O:16][C:13]1[CH:14]=[CH:15][C:10]([C:6]2[C:5]3[N:4]([N:3]=[C:2]([NH:19][C:20]4[CH:21]=[N:22][N:23]([CH2:25][C@H:26]([OH:28])[CH3:27])[CH:24]=4)[N:18]=3)[CH:9]=[CH:8][CH:7]=2)=[CH:11][CH:12]=1

Participants

7

Reactant 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 55291324(R)-1-(4-amino-1H-pyrazol-1-yl)propan-2-olHCID 59199096HCID 59199096, compound

Product 1

HCID 59199014(R)-1-(4-(8-(4-methoxyphenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino)-1H-pyrazol-1-yl)propan-2-olYield 76%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
170 °C

Procedure

A suspension of 2-iodo-8-(4-methoxyphenyl)-[1,2,4]triazolo[1,5-a]pyridine (53.6 mg, 0.153 mmol, 1 equiv), (R)-1-(4-amino-1H-pyrazol-1-yl)propan-2-ol (27 mg, 0.19 mmol, 1.2 equiv), sodium tert-butoxide (43.1 mg, 0.448 mmol, 2.94 equiv), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (15.2 mg, 0.0263 mmol, 0.172 equiv) and tris(dibenzylideneacetone)dipalladium (0) (10.5 mg, 0.0115 mmol, 0.0751 equiv) in dioxane (2 mL) was heated at 170° C. in the microwave for 15 min. The reaction mixture was partitioned between saturated aqueous sodium chloride solution (5 mL) and ethyl acetate (5 mL). The organic was separated, and the aqueous layer was extracted with ethyl acetate (2×5 mL). The collected organic was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Purification by flash column chromatography (5% methanol in dichloromethane) afforded product as a white solid (42.4 mg, 73% yield). 1H NMR (400 MHz, DMSO-d6), δ: 9.32 (s, 1H, NH), 8.64 (dd, J=6.6, 0.9 Hz, 1H), 8.13 (dd, J=8.8 Hz, 2H), 7.81 (s, 1H), 7.74 (dd, J=7.5, 0.9 Hz, 1H), 7.47 (s, 1H), 7.08 (d, J=8.9 Hz, 2H), 7.03 (t, 0.1=7.0 Hz, 1H), 4.92 (d, J=4.7 Hz, 1H, OH), 3.96 (m, 3H), 3.83 (s, 3H), 1.04 (d, J=5.8 Hz, 3H).

Workup

  1. customThe reaction mixture was partitioned between saturated aqueous sodium chloride solution (5 mL) and ethyl acetate (5 mL)
  2. customThe organic was separated
  3. extractionthe aqueous layer was extracted with ethyl acetate (2×5 mL)
  4. dry with materialThe collected organic was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by flash column chromatography (5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-7fc5c3c17754468fbfa5f7021278b1b1
Source dataset
uspto-grants-2016_09
Patent number
US09434732B2

Reaction notes

Loading…