Sodium Carbonate → (S)-tert-butyl 1-(4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy) methyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate

HRID 885739Notes

Reaction equation

HRID 885739 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([CH:22]2[CH2:24][CH2:23]2)[N:5]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[C:6]=1[C:7]1[CH:12]=[CH:11][N:10]=[C:9](Cl)[N:8]=1.[NH2:25][CH2:26][C@@H:27]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH3:28].C(N(C(C)C)CC)(C)C.C(=O)([O-])[O-].[Na+].[Na+]>CN1C(=O)CCC1>[C:32]([O:31][C:30](=[O:36])[NH:29][C@@H:27]([CH3:28])[CH2:26][NH:25][C:9]1[N:8]=[C:7]([C:6]2[N:5]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[C:4]([CH:22]3[CH2:24][CH2:23]3)=[N:3][C:2]=2[Br:1])[CH:12]=[CH:11][N:10]=1)([CH3:35])([CH3:33])[CH3:34]

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 15030821tert-butyl N-[(2S)-1-aminopropan-2-yl]carbamateHCID 866514084-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy) methyl)-1H-imidazol-5-yl)-2-chloropyrimidine

Product 1

HCID 69811029(S)-tert-butyl 1-(4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy) methyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-2-chloropyrimidine (5.50 g, 12.8 mmol), (S)-tert-butyl 1-aminopropan-2-ylcarbamate (SM-1, 2.68 g, 15.4 mmol), diisopropylethylamine (2.68 mL, 15.4 mmol) and sodium carbonate (2.71 g, 25.6 mmol) in NMP (8 mL) was heated with 110° C. oil bath for 3.5 hours and LCMS analysis of an aliquot indicated reaction completion with desired product. The reaction was allowed to cool to ambient temperature, then partitioned between EtOAc (20 mL) and water (60 mL). The EtOAc layer was washed with water (60 mL), dried (Na2SO4), and concentrated to a light yellow foam (6.89 g, 12.1 mmol). A small portion of material was further purified by flash chromatography (SiO2, EtOAc in heptane): LCMS(m/z) 567.3 (MH+), tR=1.03 minutes; 1H NMR (CDCl3, 300 MHz) δ-0.09 (s, 9H), 0.80 (t, J=8.2 Hz, 2H), 0.98-1.07 (m, 2H), 1.10-1.18 (m, 2H), 1.21 (t, J=6.5 Hz, 3H), 1.40 (s, 9H), 1.91-2.08 (m, 1H), 3.41 (t, J=8.2 Hz, 2H), 3.44-3.59 (m, 2H), 3.82-4.01 (m, 1H), 4.65-4.87 (m, 1H), 5.41-5.61 (m, 1H), 5.78-5.99 (m, 2H), 7.10 (d, J=5.0 Hz, 1H), 8.33 (d, J=5.2 Hz, 1H).

Sources & evidence

ORD record
ord-7c8e8a083ab84873bee5a3824ea3b73e
Source dataset
uspto-grants-2012_08
Patent number
US08242260B2

Reaction notes

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