Morpholine → HCID 56932980, compound

HRID 594986Notes

Reaction equation

HRID 594986 reaction equation
I[C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][CH:24]=1)[CH2:5][N:6]1[C:10]2=[N:11][C:12]([NH:15][C:16]3[CH:17]=[N:18][N:19]([CH3:21])[CH:20]=3)=[N:13][CH:14]=[C:9]2[CH:8]=[N:7]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)[O:46][C:28]2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[NH:75]1[CH2:80][CH2:79][O:78][CH2:77][CH2:76]1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[CH3:21][N:19]1[CH:20]=[C:16]([NH:15][C:12]2[N:11]=[C:10]3[N:6]([CH2:5][C:4]4[CH:3]=[C:2]([C:28]([N:75]5[CH2:80][CH2:79][O:78][CH2:77][CH2:76]5)=[O:46])[CH:24]=[CH:23][CH:22]=4)[N:7]=[CH:8][C:9]3=[CH:14][N:13]=2)[CH:17]=[N:18]1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 62657Potassium Phosphate, TribasicHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 66765269HCID 66765269, compound

Product 1

HCID 56932980HCID 56932980, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 1-(3-iodobenzyl)-N-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine (54 mg, 0.13 mmol), palladium acetate (1.4 mg, 0.05 eq), Xantphos (7.2 mg, 0.1 eq) and potassium phosphate (106 mg, 4 eq) was purged several times with carbon monoxide before addition of toluene (1 mL) and morpholine (334, 3 eq). After stirring for 2 h at 80° C., the reaction mixture was partitioned between water and DCM. The aqueous phase was extracted with DCM, the combined organic phases dried over sodium sulfate and evaporated. The residue was purified with the preparative HPLC to yield the title compound (40 mg, 96 μmol, 74%). 1H NMR (d6-DMSO) δ 9.87 (s, 1H), 8.93 (s, 1H), 8.07 (s, 1H), 8.01 (s, 1H), 7.54 (s, 1H), 7.46-7.36 (m, 2H), 7.35-7.25 (m, 2H), 5.62 (s, 2H), 3.82 (s, 3H), 3.68-3.08 (m, 8H); LC-MS method B, (ES+) 419.2, RT=6.42 min.

Workup

  1. customwas purged several times with carbon monoxide
  2. customthe reaction mixture was partitioned between water and DCM
  3. extractionThe aqueous phase was extracted with DCM
  4. dry with materialthe combined organic phases dried over sodium sulfate
  5. customevaporated
  6. customThe residue was purified with the preparative HPLC

Sources & evidence

ORD record
ord-f9b2c227766a40b4bf2ac63db65b89de
Source dataset
uspto-grants-2016_01
Patent number
US09242987B2

Reaction notes

Loading…