Sodium Carbonate → HCID 118436652, compound

HRID 1775466Notes

Reaction equation

HRID 1775466 reaction equation
Cl[C:2]1[C:3]2[CH2:16][CH2:15][N:14]([C@:17]3([CH3:29])[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18]3)[C:4]=2[N:5]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[N:7]=1.CC1(C)C(C)(C)OB([C:38]2[CH:39]=[N:40][C:41]([NH2:44])=[N:42][CH:43]=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>[NH2:44][C:41]1[N:42]=[CH:43][C:38]([C:2]2[C:3]3[CH2:16][CH2:15][N:14]([C@:17]4([CH3:29])[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:26])([CH3:28])[CH3:27])=[O:23])[CH2:18]4)[C:4]=3[N:5]=[C:6]([N:8]3[CH2:9][CH2:10][O:11][CH2:12][CH2:13]3)[N:7]=2)=[CH:39][N:40]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 177502122-Aminopyrimidine-5-boronic acid, pinacol esterHCID 118436036HCID 118436036, compound

Product 1

HCID 118436652HCID 118436652, compoundYield 88%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of tert-butyl(3R)-3-[4-chloro-2-(morpholin-4-yl)-5,6-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-3-methylpyrrolidine-1-carboxylate (150 mg, 0.354 mmol) in dioxane (3 mL) was added 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine (104 mg, 0.471 mmol), and 1 M aqueous Na2CO3 (1.3 mL, 51.3 mmol). Nitrogen was bubbled through the suspension for a few minutes before PdCl2(dppf)2-DCM (24 mg, 0.029 mmol) was added. The vial was crimp sealed and the reaction was heated at 120° C. for 30 min in a microwave reactor. The mixture was partitioned between EtOAc and aqueous NaHCO3. The aqueous layer was extracted with EtOAc (2x). The combined organic layers were dried over MgSO4 and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using a gradient of 0-10% (MeOH with 10% NH4OH)/(EtOAc/DCM, 1:1) to give 150 mg (88%) of the title compound as a crisp foam (˜85% pure). This material was taken into the next step without further purification. 1H NMR (400 MHz, 80° C., DMSO-d6) δ 8.72 (s, 2 H), 6.60 (br s, 2 H), 3.80-3.62 (m, 11 H), 3.54 (q, J=8.9 Hz, 1 H), 3.42-3.34 (m, 1 H), 3.33-3.23 (m, 1 H), 3.09 (t, J=8.1 Hz, 2 H), 2.44-2.34 (m, 1 H), 2.08-1.99 (m, 1 H), 1.42 (s, 9 H), 1.31 (s, 3 H).

Workup

  1. additionwas added
  2. customThe vial was crimp sealed
  3. customThe mixture was partitioned between EtOAc and aqueous NaHCO3
  4. extractionThe aqueous layer was extracted with EtOAc (2x)
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-82b08505562f48d999b5bcfd981f4f06
Source dataset
uspto-grants-2016_02
Patent number
US09260439B2

Reaction notes

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