Morpholine → HCID 56932980, compound

HRID 577265Notes

Reaction equation

HRID 577265 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 (33 μL, 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-a2ea5f59746b466183c5e9fc1e33c5e5
Source dataset
uspto-grants-2015_05
Patent number
US09040545B2

Reaction notes

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