Diisopropylethylamine → (S)-tert-butyl 2-((4-(4-(4-(5-(cyclopropylethynyl)pyrimidin-2-yl)piperazin-1-yl)-1,3,5-triazin-2-ylamino)-1H-pyrazol-1-yl)methyl)morpholine-4-carboxylate

HRID 522661Notes

Reaction equation

HRID 522661 reaction equation
Cl.[CH:2]1([C:5]#[C:6][C:7]2[CH:8]=[N:9][C:10]([N:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)=[N:11][CH:12]=2)[CH2:4][CH2:3]1.Cl[C:20]1[N:25]=[CH:24][N:23]=[C:22]([NH:26][C:27]2[CH:28]=[N:29][N:30]([CH2:32][C@H:33]3[O:38][CH2:37][CH2:36][N:35]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:34]3)[CH:31]=2)[N:21]=1.C(N(C(C)C)CC)(C)C>>[CH:2]1([C:5]#[C:6][C:7]2[CH:8]=[N:9][C:10]([N:13]3[CH2:14][CH2:15][N:16]([C:20]4[N:25]=[CH:24][N:23]=[C:22]([NH:26][C:27]5[CH:28]=[N:29][N:30]([CH2:32][C@H:33]6[O:38][CH2:37][CH2:36][N:35]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:34]6)[CH:31]=5)[N:21]=4)[CH2:17][CH2:18]3)=[N:11][CH:12]=2)[CH2:4][CH2:3]1

Participants

4

Reactant 3

HCID 81531DiisopropylethylamineHCID 118022859(S)-tert-butyl 2-((4-(4-chloro-1,3,5-triazin-2-ylamino)-1H-pyrazol-1-yl)methyl)-morpholine-4-carboxylateHCID 1180236485-(cyclopropylethynyl)-2-(piperazin-1-yl)pyrimidine HCl salt

Product 1

HCID 118022800(S)-tert-butyl 2-((4-(4-(4-(5-(cyclopropylethynyl)pyrimidin-2-yl)piperazin-1-yl)-1,3,5-triazin-2-ylamino)-1H-pyrazol-1-yl)methyl)morpholine-4-carboxylateYield 94%

Procedure

To a solution of 5-(cyclopropylethynyl)-2-(piperazin-1-yl)pyrimidine HCl salt (172 mg, 0.44 mmol) and (s)-tert-butyl 2-((4-(4-chloro-1,3,5-triazin-2-ylamino)-1H-pyrazol-1-yl)methyl)morpholine-4-carboxylate was added diisopropylethylamine (169 mg, 1.311 mmol), and the reaction mixture was stirred at room temperature. LCMS showed the reaction was completed. The mixture was concentrated, and the residue was purified by silica gel chromatography, eluting with petroleum ether:ethyl acetate=1:2, to afford (S)-tert-butyl 2-((4-(4-(4-(5-(cyclopropylethynyl)pyrimidin-2-yl)piperazin-1-yl)-1,3,5-triazin-2-ylamino)-1H-pyrazol-1-yl)methyl)morpholine-4-carboxylate (240 mg, 94%) as a yellowish solid. MS (ES+): C29H37N11O3 requires: 587, found: 588 [M+H]+.

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was purified by silica gel chromatography
  3. washeluting with petroleum ether

Sources & evidence

ORD record
ord-50c30914b2e64c34b300847187868483
Source dataset
uspto-grants-2016_05
Patent number
US09334263B2

Reaction notes

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