Sodium Carbonate → HCID 118436056, compound

HRID 1775476Notes

Reaction equation

HRID 1775476 reaction equation
Cl[C:2]1[C:3]2[CH2:16][CH2:15][N:14]([C@@:17]3([CH3:25])[CH2:21][CH2:20][N:19]([C:22]([O-:24])=[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:34]2[CH:35]=[N:36][C:37]([NH2:40])=[N:38][CH:39]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.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:36]=[CH:35][C:34]([C:2]2[C:3]3[CH2:16][CH2:15][N:14]([C@@:17]4([CH3:25])[CH2:21][CH2:20][N:19]([C:22]([O:24][C:3]([CH3:16])([CH3:4])[CH3:2])=[O:23])[CH2:18]4)[C:4]=3[N:5]=[C:6]([N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)[N:7]=2)=[CH:39][N:38]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 177502122-Aminopyrimidine-5-boronic acid, pinacol esterHCID 131734744HCID 131734744, compound

Product 1

HCID 118436056HCID 118436056, compoundYield 803.2%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

Two separate reaction vessels containing a yellow mixture of (3S)-3-[4-chloro-2-(morpholin-4-yl)-5,6-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-3-methylpyrrolidine-1-carboxylate (prepared from 2-[4,6-dichloro-2-(morpholin-4-yl)pyrimidin-5-yl]ethanol (Preparation 1) and tert-butyl(3S)-3-amino-3-methylpyrrolidine-1-carboxylate (Preparation 4)) (3500 mg, 8.256 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine (2.37 g, 10.7 mmol) and Na2CO3 (2630 mg, 24.8 mmol) in 1,4-dioxane (90 mL) and water (30 mL), were prepared. To each reaction mixture was added Pd(dppf)Cl2-DCM (362 mg, 0.495 mmol) in one portion at 15° C. under nitrogen atmosphere, and the reaction mixtures were heated at 120° C. for 16 h. The reaction mixtures were combined and concentrated to give 16 g of a black gum. The material was purified by silica gel column chromatography eluting with a gradient of 30-75% EtOAc in petroleum ether, followed by a gradient of 0-1% MeOH in EtOAc to give the title compound (7.0 g, 87%) as a yellow solid. 1H NMR (400 MHz, 80° C., DMSO-d6) δ 8.73 (s, 2 H), 6.61 (br s, 2 H), 3.80-3.63 (m, 11 H), 3.54 (q, J=8.7 Hz, 1 H), 3.42-3.35 (m, 1 H), 3.33-3.25 (m, 1 H), 3.09 (t, J=8.2 Hz, 2 H), 2.44-2.35 (m, 1 H), 2.07-2.00 (m, 1 H), 1.42 (s, 9 H), 1.32 (s, 3 H). m/z (APCI+) for C24H34N8O3 483.2 [M+H]+.

Workup

  1. customTwo separate
  2. customreaction vessels
  3. additioncontaining
  4. customwere prepared
  5. customthe reaction mixtures
  6. customThe reaction mixtures
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-09290485a0f04b37899ca17684203048
Source dataset
uspto-grants-2016_02
Patent number
US09260439B2

Reaction notes

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