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 1043720Notes

Reaction equation

HRID 1043720 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-eeaa258ec796491f93d6e3a845ee23a8
Source dataset
uspto-grants-2013_10
Patent number
US08563553B2

Reaction notes

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