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

HRID 527098Notes

Reaction equation

HRID 527098 reaction equation
Cl[C:2]1N=[C:6]([C:8]2(N)CC(C)CC(N)C2)[C:5]([F:17])=[CH:4][N:3]=1.[Cl:18][C:19]1[N:24]=[C:23]([NH:25][CH:26]2[CH2:31][CH:30]([CH3:32])[CH2:29][CH:28]([NH2:33])[CH2:27]2)[C:22]([F:34])=[CH:21][N:20]=1.C(N1C=CN=C1)(N1C=CN=C1)=[O:36].CCN(C(C)C)C(C)C.Cl.F[C@H]1CCNC1>C1COCC1>[Cl:18][C:19]1[N:24]=[C:23]([NH:25][CH:26]2[CH2:31][CH:30]([CH3:32])[CH2:29][CH:28]([NH:33][C:2]([N:3]3[CH2:8][CH2:6][C@H:5]([F:17])[CH2:4]3)=[O:36])[CH2:27]2)[C:22]([F:34])=[CH:21][N:20]=1

Participants

7

Reactant 5

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 16217739(s)-3-Fluoropyrrolidine hydrochlorideHCID 86667457N1-(2-chloro-5-fluoropyrimidin-4-yl)-5-methylcyclohexane-1,3-diamineHCID 87340099(2-Chloro-5-fluoropyrimidin-4-yl)-5-methylcyclohexane-1,3-diamine

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 AP-(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-cc49340ed1b4406f85483772f697088f
Source dataset
uspto-grants-2016_05
Patent number
US09345708B2

Reaction notes

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