Sodium Hydroxide → 4-(1-((9-methyl-6-morpholino-2-(1H-pyrrolo[2,3-c]pyridin-4-yl)-9H-purin-8-yl)methyl)piperidin-4-yl)morpholine

HRID 1922890Notes

Reaction equation

HRID 1922890 reaction equation
[CH3:1][N:2]1[C:10]([CH2:11][N:12]2[CH2:17][CH2:16][CH:15]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[CH2:14][CH2:13]2)=[N:9][C:8]2[C:3]1=[N:4][C:5]([Sn](CCCC)(CCCC)CCCC)=[N:6][C:7]=2[N:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.Br[C:44]1[CH:49]=[N:48][CH:47]=[C:46]2[N:50](S(C3C=CC=CC=3)(=O)=O)[CH:51]=[CH:52][C:45]=12.[OH-].[Na+]>O1CCOCC1.C(O)C.[Cu]I.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>[CH3:1][N:2]1[C:10]([CH2:11][N:12]2[CH2:13][CH2:14][CH:15]([N:18]3[CH2:19][CH2:20][O:21][CH2:22][CH2:23]3)[CH2:16][CH2:17]2)=[N:9][C:8]2[C:3]1=[N:4][C:5]([C:44]1[CH:49]=[N:48][CH:47]=[C:46]3[NH:50][CH:51]=[CH:52][C:45]=13)=[N:6][C:7]=2[N:24]1[CH2:25][CH2:26][O:27][CH2:28][CH2:29]1

Participants

8

Reactant 3

HCID 14798Sodium HydroxideHCID 583564464-bromo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-c]pyridineHCID 596061644-(1-((9-methyl-6-morpholino-2-(tributylstannyl)-9H-purin-8-yl)methyl)piperidin-4-yl)morpholine

Product 1

HCID 596055054-(1-((9-methyl-6-morpholino-2-(1H-pyrrolo[2,3-c]pyridin-4-yl)-9H-purin-8-yl)methyl)piperidin-4-yl)morpholine

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
110 °C

Procedure

To a degassed mixture of 4-(1-((9-methyl-6-morpholino-2-(tributylstannyl)-9H-purin-8-yl)methyl)piperidin-4-yl)morpholine (859 mg, 1.24 mmol), 4-bromo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-c]pyridine (385 mg, 1.14 mmol), copper(I)iodide (326 mg, 1.71 mmol) in 1,4-dioxane (10 mL) was added Pd(PPh3)4 (100 mg, 0.09 mmol). The reaction mixture was stirred at 110° C. for 18 hours. The reaction mixture was concentrated and then dissolved in DCM and filtered through a column of silica gel (20% MeOH in DCM). The elutant was concentrated to give a yellow paste which was taken up in ethanol (2 mL) and 1,4-dioxane (3 mL). A 12 M aqueous NaOH solution (0.5 mL) was then added and the resulting mixture was stirred at room temperature for 1 hour. The reaction mixture was then concentrated and the crude product was purified by flash chromatography using a Biotage KP-NH column (10% MeOH in DCM) followed by RP-HPLC to give 124. LCMS: M+H+=518.3. 1H-NMR (400 MHz, DMSO-d6): δ 11.70 (s, 1H), 9.14 (s, 1H), 8.79 (s, 1H), 7.70 (m, 1H), 7.43 (m, 1H), 4.30 (s, br, 4H), 3.88 (s, 3H), 3.78 (m, 4H), 3.70 (s, 2H), 3.54 (m, 4H), 2.86 (m, 2H), 2.43 (m, 4H), 2.09 (m, 2H), 1.75 (m, 2H), 1.36 (m, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutiondissolved in DCM
  3. filtrationfiltered through a column of silica gel (20% MeOH in DCM)
  4. concentrationThe elutant was concentrated
  5. customto give a yellow paste which
  6. stirringthe resulting mixture was stirred at room temperature for 1 hour
  7. concentrationThe reaction mixture was then concentrated
  8. customthe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-ad7669677b14413094bc7b1bdd81993c
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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