1,1'-Carbonyldiimidazole → (3S)-N-(3-((2-chloro-5-fluoropyrimidin-4-yl)amino)-5-methylcyclohexyl)-3-fluoropyrrolidine-1-carboxamide

HRID 75057Notes

Reaction equation

HRID 75057 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH:9]2[CH2:14][CH:13]([CH3:15])[CH2:12][CH:11]([NH2:16])[CH2:10]2)[C:5]([F:17])=[CH:4][N:3]=1.[C:18](N1C=CN=C1)(N1C=CN=C1)=[O:19].CCN(C(C)C)C(C)C.Cl.[F:40][C@H:41]1[CH2:45][CH2:44][NH:43][CH2:42]1>C1COCC1>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH:9]2[CH2:14][CH:13]([CH3:15])[CH2:12][CH:11]([NH:16][C:18]([N:43]3[CH2:44][CH2:45][C@H:41]([F:40])[CH2:42]3)=[O:19])[CH2:10]2)[C:5]([F:17])=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 16217739(s)-3-Fluoropyrrolidine hydrochlorideHCID 86667457N1-(2-chloro-5-fluoropyrimidin-4-yl)-5-methylcyclohexane-1,3-diamine2×

Product 1

HCID 86667456(3S)-N-(3-((2-chloro-5-fluoropyrimidin-4-yl)amino)-5-methylcyclohexyl)-3-fluoropyrrolidine-1-carboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N1-(2-chloro-5-fluoropyrimidin-4-yl)-5-methylcyclohexane-1,3-diamine, 76b, (0.14 g. 0.54 mmol) in THF (2.5 ml) was added carbonyldiimidazole (0.10 g, 0.60 mmol) and iPr2NEt (0.28 mL, 1.62 mmol). The reaction was aged 2 hours at room temp, and treated with (S)-3-fluoropyrrolidine hydrochloride (0.07 g, 0.54 mmol). The reaction was stirred at room temperature for 2 days and then concentrated to dryness to afford 202 mg of (3S)—N-(3-((2-chloro-5-fluoropyrimidin-4-yl)amino)-5-methylcyclohexyl)-3-fluoropyrrolidine-1-carboxamide which was used without purification: LCMS RT=2.46 (M+1) 374.2, (M−1) 372.

Workup

  1. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-419d09ac130d4691be69c1166f9b7b44
Source dataset
uspto-grants-2014_09
Patent number
US08829007B2

Reaction notes

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