1,2-Dichloroethane → Hydrochloric Acid

HRID 1050548Notes

Reaction equation

HRID 1050548 reaction equation
[CH3:1][N:2]([CH3:35])[C:3](=[O:34])[NH:4][C@@H:5]1[CH2:10][CH2:9][CH2:8][N:7]([C:11]2[N:12]=[C:13]([NH:20][C:21]3[CH:26]=[CH:25][C:24]([C:27]4([CH3:33])[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]4)=[CH:23][CH:22]=3)[C:14]([C:17]([NH2:19])=[O:18])=[N:15][CH:16]=2)[CH2:6]1.CCN(C(C)C)C(C)C.[C:45]1(=O)[CH2:49][CH2:48][CH2:47][CH2:46]1.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[Cl:69]CCCl>O1CCOCC1.CO>[CH:45]1([N:30]2[CH2:29][CH2:28][C:27]([C:24]3[CH:25]=[CH:26][C:21]([NH:20][C:13]4[C:14]([C:17]([NH2:19])=[O:18])=[N:15][CH:16]=[C:11]([N:7]5[CH2:8][CH2:9][CH2:10][C@@H:5]([NH:4][C:3]([N:2]([CH3:1])[CH3:35])=[O:34])[CH2:6]5)[N:12]=4)=[CH:22][CH:23]=3)([CH3:33])[CH2:32][CH2:31]2)[CH2:49][CH2:48][CH2:47][CH2:46]1.[ClH:69]

Participants

10

Reactant 6

HCID 111,2-DichloroethaneHCID 176Acetic AcidHCID 8452CyclopentanoneHCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 118114473HCID 118114473, compound

Product 2

HCID 313Hydrochloric AcidYield 37%HCID 118114676HCID 118114676, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

(R)-5-(3-(3,3-Dimethylureido)piperidin-1-yl)-3-(4-(4-methylpiperidin-4-yl)phenylamino)pyrazine-2-carboxamide (289) (190 mg, 0.4 mmol) was dissolved in 20 mL DCE and 20 mL dioxane. To it were added DIEA (350 μL, 2.0 mmol) and cyclopentanone (710 μL, 8.0 mmol). The mixture was stirred at RT for 2 hours, and to it were added HOAc (250 μL, 4.0 mmol) and NaBH(OAc)3 (430 mg, 2.0 mmol). The mixture was stirred at RT for 1.5 hour. It was diluted with 10 mL MeOH, concentrated in vacuo, acidified with 0.5 mL TFA, and directly subjected to reverse phase prep HPLC using 5 mM HCl (aq) and neat MeCN as mobile phases to isolate (R)-3-(4-(1-cyclopentyl-4-methylpiperidin-4-yl)phenylamino)-5-(3-(3,3-dimethylureido)piperidin-1-yl)pyrazine-2-carboxamide (290) as HCl salt (82 mg, 37%). MS found for C30H44N8O2 as (M+H)+ 549.6. UV: λ=268, 278, 306, 336, 373 nm. Proton NMR (CD3OD): δ 7.71-7.63 (3H, m), 7.36-7.33 (2H, m), 4.38-4.32 (1H, m), 4.22 (1H, m), 3.77 (1H, m), 3.66-3.50 (2H, m), 3.28-3.10 (2H, m), 2.89 (6H, s), 2.86-2.80 (2H, m), 2.64 (1H, m), 2.23-1.62 (16H, m), 1.42-1.26 (3H, s) ppm.

Workup

  1. stirringThe mixture was stirred at RT for 1.5 hour
  2. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-49c2b5b6d2c348cb9016d38b21d2b308
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

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