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

HRID 522634Notes

Reaction equation

HRID 522634 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]3[N:19]=[CH:18][N:17]=[C:16]([NH:20][C:21]4[CH:22]=[N:23][N:24]([CH2:26][C@H:27]5[O:32][CH2:31][CH2:30][N:29]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:28]5)[CH:25]=4)[N:15]=3)[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[Br-].[C:41]1([CH:47]([Zn+])[CH3:48])[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1>C1COCC1.C(OCC)(=O)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[C:41]1([CH:47]([C:2]2[CH:3]=[N:4][C:5]([N:8]3[CH2:13][CH2:12][N:11]([C:14]4[N:19]=[CH:18][N:17]=[C:16]([NH:20][C:21]5[CH:22]=[N:23][N:24]([CH2:26][C@H:27]6[O:32][CH2:31][CH2:30][N:29]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:28]6)[CH:25]=5)[N:15]=4)[CH2:10][CH2:9]3)=[N:6][CH:7]=2)[CH3:48])[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1

Participants

6

Reactant 2

HCID 118023021(S)-tert-butyl 2-((4-(4-(4-(5-bromopyrimidin-2-yl)piperazin-1-yl)-1,3,5-triazin-2-ylamino)-1H-pyrazol-1-yl)methyl)-morpholine-4-carboxylateHCID 178462437HCID 178462437, compound

Product 1

HCID 118023199(2S)-tert-butyl 2-((4-(4-(4-(5-(1-phenylethyl)pyrimidin-2-yl)piperazin-1-yl)-1,3,5-triazin-2-ylamino)-1H-pyrazol-1-yl)methyl)morpholine-4-carboxylate

Reagents, catalysts & solvents 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of (S)-tert-butyl 2-((4-(4-(4-(5-bromopyrimidin-2-yl)piperazin-1-yl)-1,3,5-triazin-2-ylamino)-1H-pyrazol-1-yl)methyl)morpholine-4-carboxylate (100 mg, 0.17 mmol) and Pd(Amphos)Cl2 (11.7 mg, 0.17 mmol) in THF (2 mL, dried) was dropwise added a solution of (1-phenylethyl)zinc(II) bromide in THF (7.0 mL, 0.5 M, 3.4 mmol). The reaction mixture was stirred at 70° C. for 1 hour under N2, then cooled to room temperature and diluted with ethyl acetate (50 mL). After filtration, the filtrate was concentrated to afford (2S)-tert-butyl 2-((4-(4-(4-(5-(1-phenylethyl)pyrimidin-2-yl)piperazin-1-yl)-1,3,5-triazin-2-ylamino)-1H-pyrazol-1-yl)methyl)morpholine-4-carboxylate as a white solid (130 mg, crude), which was directly used in the next step without further purification. MS (ES+) C32H41N11O3 requires: 627, found: 628 [M+H]+.

Workup

  1. temperaturecooled to room temperature
  2. filtrationAfter filtration
  3. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-7d47f8c24e8645a28bb48578c1f61326
Source dataset
uspto-grants-2016_05
Patent number
US09334263B2

Reaction notes

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