Dichloromethane → HCID 90314482, compound

HRID 1523855Notes

Reaction equation

HRID 1523855 reaction equation
Br[C:2]1[CH:25]=[CH:24][CH:23]=[CH:22][C:3]=1[CH2:4][S:5]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:10][CH2:9]1)(=[O:7])=[O:6].[F:26][C:27]1[CH:32]=[C:31](B2OC(C)(C)C(C)(C)O2)[CH:30]=[CH:29][C:28]=1[C:42]1[N:43]=[CH:44][C:45]([NH2:48])=[N:46][CH:47]=1.C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:48][C:45]1[N:46]=[CH:47][C:42]([C:28]2[C:27]([F:26])=[CH:32][C:31]([C:2]3[CH:25]=[CH:24][CH:23]=[CH:22][C:3]=3[CH2:4][S:5]([N:8]3[CH2:13][CH2:12][CH:11]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:10][CH2:9]3)(=[O:7])=[O:6])=[CH:30][CH:29]=2)=[N:43][CH:44]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 903122765-(2-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-phenyl)-pyrazin-2-amineHCID 90327746HCID 90327746, compound

Product 1

HCID 90314482HCID 90314482, compoundYield 76.3%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of tert-butyl (1-((2-bromobenzyl)sulfonyl)piperidin-4-yl)carbamate (200 mg, 0.46 mmol), 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine (175 mg, 0.55 mmol), Pd(dppf)Cl2.CH2Cl2 (34 mg, 0.046 mmol) and Na2CO3 (150 mg, 1.36 mmol) in dry DMF (15 mL) was stirred at 130° Celsius under N2. After 5 hours, the solvent was removed under vacuum and the residue was subjected to FCC purification to give tert-butyl 1-((4′-(5-aminopyrazin-2-yl)-5′-fluorobiphenyl-2-yl)methylsulfonyl)piperidin-4-ylcarbamate (190 mg, 76%). MS (ESI): mass calcd. for C27H32FN5O2S, 541.22; m/z found, 542.1 [M+H]+. 1H NMR (300 MHz, DMSO-d6) δ 8.39 (s, 1H), 8.03 (s, 1H), 7.95 (s, 1H), 7.78-7.29 (m, 7H), 6.87 (d, J=5.2, 1H), 6.73 (s, 2H), 4.34 (s, 2H), 3.45-3.33 (m, 3H), 2.85-2.75 (m, 2H), 1.72 (d, J=12.4, 2H), 1.45-1.30 (m, 11H).

Workup

  1. customthe solvent was removed under vacuum
  2. customthe residue was subjected to FCC purification

Sources & evidence

ORD record
ord-314e7ede1c6f42fc8737531e63b091ae
Source dataset
uspto-grants-2015_07
Patent number
US09079866B2

Reaction notes

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