Sodium Carbonate → HCID 68748691, compound

HRID 1051796Notes

Reaction equation

HRID 1051796 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[Cl:12])[CH:5]=[C:4]([C@@H:13]([NH:15][C:16]2[N:24]=[CH:23][N:22]=[C:21]3[C:17]=2[N:18]=[CH:19][N:20]3[CH2:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)[CH3:14])[N:3]=1.[CH3:34]B(O)O.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:33][O:32][C:29]1[CH:30]=[CH:31][C:26]([CH2:25][N:20]2[CH:19]=[N:18][C:17]3[C:21]2=[N:22][CH:23]=[N:24][C:16]=3[NH:15][C@H:13]([C:4]2[N:3]=[C:2]([CH3:34])[C:11]3[C:6]([CH:5]=2)=[CH:7][CH:8]=[CH:9][C:10]=3[Cl:12])[CH3:14])=[CH:27][CH:28]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 139377Methylboronic AcidHCID 86665021HCID 86665021, compound

Product 1

HCID 68748691HCID 68748691, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

(S)-9-(4-Methoxybenzyl)-N-(1-(1,8-dichloroisoquinolin-3-yl)ethyl)-9H-purin-6-amine (1) (2.0 g, 4.2 mmol, 1.0 eq), methylboronic acid (277 mg, 4.62 mmol, 1.1 eq), Pd (PPh3)4(485 mg, 0.42 mmol, 0.1 eq) and Na2CO3(1.34 g, 12.6 mmol, 3.0 eq) were suspended in a mixture of 1,4-dioxane (30 mL) and water (10 mL). The resulting mixture was degassed and back-filled with argon three times and then stirred at reflux under argon for 16 h. The mixture was allowed to cool to RT, concentrated in vacuo and the residue was purified by column chromatography on silica gel (1-3% MeOH-DCM) to afford the product, (S)-9-(4-methoxybenzyl)-N-(1-(8-chloro-1-methylisoquinolin-3-yl)ethyl)-9H-purin-6-amine (168). Compound 168 was then converted to compound 169 using the analogous procedures for the synthesis of 151 in Example 91 except that pyridin-3-ylboronic acid was used in place of 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. The PMB group of compound 169 was then subsequently deprotected using Method L to afford compound 170. ESI-MS m/z: 382.2 [M+H]+.

Workup

  1. customThe resulting mixture was degassed
  2. additionback-filled with argon three times
  3. temperatureat reflux under argon for 16 h
  4. concentrationconcentrated in vacuo
  5. customthe residue was purified by column chromatography on silica gel (1-3% MeOH-DCM)

Sources & evidence

ORD record
ord-300fae7c5cea4a7a994b1d29e8be59bb
Source dataset
uspto-grants-2016_07
Patent number
US09388183B2

Reaction notes

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