Sodium Carbonate → HCID 118436211, compound

HRID 1775479Notes

Reaction equation

HRID 1775479 reaction equation
Cl.Cl[C:3]1[C:4]2[CH2:18][CH2:17][N:16]([C@@:19]3([CH3:31])[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20]3)[C:5]=2[N:6]=[C:7]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][C@@H:10]2[CH3:15])[N:8]=1.CC1(C)C(C)(C)OB([C:40]2[CH:41]=[N:42][C:43]([NH2:46])=[N:44][CH:45]=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>[NH2:46][C:43]1[N:44]=[CH:45][C:40]([C:3]2[C:4]3[CH2:18][CH2:17][N:16]([C@@:19]4([CH3:31])[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:29])([CH3:30])[CH3:28])=[O:25])[CH2:20]4)[C:5]=3[N:6]=[C:7]([N:9]3[CH2:14][CH2:13][O:12][CH2:11][C@@H:10]3[CH3:15])[N:8]=2)=[CH:41][N:42]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 177502122-Aminopyrimidine-5-boronic acid, pinacol esterHCID 118436576HCID 118436576, compound

Product 1

HCID 118436211HCID 118436211, compoundYield 91.4%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a vial containing tert-butyl(3S)-3-{4-chloro-2-[(3S)-3-methylmorpholin-4-yl]-5,6-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-3-methylpyrrolidine-1-carboxylate hydrochloride (3796 mg, 8.68 mmol) in 1,4-dioxane (41.2 mL) was added 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine (2492 mg, 11.28 mmol), and 1 M aqueous Na2CO3 (26 mL). Nitrogen was bubbled through the suspension for a few minutes before PdCl2(dppf)-DCM (516 mg, 0.632 mmol) was added and the mixture was heated in a microwave reactor at 120° C. for 30 min. The mixture was filtered through a pad of Celite® rinsing with EtOAc, and the filtrate was concentrated. The residue was purified by ISCO (80 g cartridge) using a gradient of 25-100% EtOAc/heptanes to give the title compound (3.94 g, 91%) as a yellow foamy solid. 1H NMR (400 MHz, DMSO-d6) δ 8.73 (s, 2 H), 6.60 (s, 2 H), 4.64-4.54 (m, 1 H), 4.23 (dd, J=13.5, 2.3 Hz, 1 H), 3.89 (dd, J=11.2, 3.4 Hz, 1 H), 3.79-3.35 (m, 8 H), 3.33-3.24 (m, 1 H), 3.19-3.05 (m, 3 H), 2.44-2.30 (m, 1 H), 2.10-1.95 (m, 1 H), 1.42 (s, 9 H), 1.32 (s, 3 H), 1.21 (d, J=6.7 Hz, 3 H). m/z (APCI+) for C25H36N8O3 497.6 (M+H)+.

Workup

  1. additionwas added
  2. filtrationThe mixture was filtered through a pad of Celite®
  3. washrinsing with EtOAc
  4. concentrationthe filtrate was concentrated
  5. customThe residue was purified by ISCO (80 g cartridge)

Sources & evidence

ORD record
ord-62ca8259bca2459684dcedc7f0b53737
Source dataset
uspto-grants-2016_02
Patent number
US09260439B2

Reaction notes

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