Sodium Carbonate → tert-butyl(3S)-3-[4-(2-aminopyrimidin-5-yl)-2-(methylsulfanyl)-5,6-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-3-methylpyrrolidine-1-carboxylate

HRID 1775493Notes

Reaction equation

HRID 1775493 reaction equation
Cl[C:2]1[C:3]2[CH2:12][CH2:11][N:10]([C@@:13]3([CH3:25])[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14]3)[C:4]=2[N:5]=[C:6]([S:8][CH3:9])[N:7]=1.CC1(C)C(C)(C)OB([C:34]2[CH:35]=[N:36][C:37]([NH2:40])=[N:38][CH:39]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[NH2:40][C:37]1[N:38]=[CH:39][C:34]([C:2]2[C:3]3[CH2:12][CH2:11][N:10]([C@@:13]4([CH3:25])[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14]4)[C:4]=3[N:5]=[C:6]([S:8][CH3:9])[N:7]=2)=[CH:35][N:36]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 177502122-Aminopyrimidine-5-boronic acid, pinacol esterHCID 118436106tert-butyl(3S)-3-[4-chloro-2-(methylsulfanyl)-5,6-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-3-methylpyrrolidine-1-carboxylate

Product 1

HCID 118436590tert-butyl(3S)-3-[4-(2-aminopyrimidin-5-yl)-2-(methylsulfanyl)-5,6-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-3-methylpyrrolidine-1-carboxylateYield 58%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a suspension of tert-butyl(3S)-3-[4-chloro-2-(methylsulfanyl)-5,6-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-3-methylpyrrolidine-1-carboxylate (1.24 g, 3.22 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine (1.0 g, 4.6 mmol) in dioxane (16 mL) was added 1 M Na2CO3 solution (13 mL, 12.9 mmol) at room temperature. The reaction mixture was purged with nitrogen for a few minutes before adding PdCl2(dppf)-DCM (395 mg, 0.484 mmol). The reaction mixture was heated at 120° C. for 40 h in a microwave reactor. The mixture was filtered through a pad of Celite® rinsing with EtOAc several times, concentrated and purified via ISCO normal phase silica gel chromatography (40 g column) with a 0-100% gradient of EtOAc/Heptane to give the title compound (828 mg, 58%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.72 (d, J=4.6 Hz, 2 H), 7.06 (s, 2 H), 3.79-3.64 (m, 3 H), 3.63-3.51 (m, 1 H), 3.39-3.34 (m, 2 H), 3.21-3.14 (m, 2 H), 2.45 (s, 3 H), 2.41-2.27 (m, 1 H), 2.10-1.99 (m, 1 H), 1.40 (s, 9 H), 1.28 (s, 3 H). m/z (APCI+) for C21H29N7O2S 444.2 (M+H)+.

Workup

  1. customThe reaction mixture was purged with nitrogen for a few minutes
  2. filtrationThe mixture was filtered through a pad of Celite®
  3. washrinsing with EtOAc several times
  4. concentrationconcentrated
  5. custompurified via ISCO normal phase silica gel chromatography (40 g column) with a 0-100% gradient of EtOAc/Heptane

Sources & evidence

ORD record
ord-6c2d406434374a21a4cdc5e24875d078
Source dataset
uspto-grants-2016_02
Patent number
US09260439B2

Reaction notes

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