1,2-Dichloroethane → Hydrochloric Acid

HRID 1050552Notes

Reaction equation

HRID 1050552 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]3[C:15]([C:33]([NH2:35])=[O:34])=[N:16][CH:17]=[C:18]([N:20]4[CH2:25][CH2:24][CH2:23][C@@H:22]([N:26]([CH3:32])[C:27]([N:29]([CH3:31])[CH3:30])=[O:28])[CH2:21]4)[N:19]=3)=[CH:9][CH:8]=2)[CH2:3][CH2:2]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:1]2[CH2:2][CH2:3][CH:4]([C:7]3[CH:8]=[CH:9][C:10]([NH:13][C:14]4[C:15]([C:33]([NH2:35])=[O:34])=[N:16][CH:17]=[C:18]([N:20]5[CH2:25][CH2:24][CH2:23][C@@H:22]([N:26]([CH3:32])[C:27]([N:29]([CH3:30])[CH3:31])=[O:28])[CH2:21]5)[N:19]=4)=[CH:11][CH:12]=3)[CH2:5][CH2:6]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 118114608HCID 118114608, compound

Product 2

HCID 313Hydrochloric AcidYield 29%HCID 118114848HCID 118114848, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

Crude (R)-3-(4-(piperidin-4-yl)phenylamino)-5-(3-(1,3,3-trimethylureido)piperidin-1-yl)pyrazine-2-carboxamide (297) (100 mg, 0.18 mmol) was dissolved in 10 mL DCE and 10 mL dioxane. To it were added DIEA (160 μL, 0.90 mmol) and cyclopentanone (320 μL, 3.60 mmol). The mixture was stirred at RT for 2 hours, and to it were added HOAc (100 μL, 1.8 mmol) and NaBH(OAc)3 (190 mg, 0.90 mmol). The mixture was stirred at RT for overnight. 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-cyclopentylpiperidin-4-yl)phenylamino)-5-(3-(1,3,3-trimethylureido)piperidin-1-yl)pyrazine-2-carboxamide (298) as HCl salt (29 mg, 29%). MS found for C30H44N8O2 as (M+H)+ 549.6. UV: λ=269, 276, 306, 335, 373 nm. Proton NMR (CD3OD): δ 7.64 (1H, s), 7.57 (2H, d, J=8.5 Hz), 7.21 (2H, d, J=8.5 Hz), 4.53 (1H, m), 4.35 (1H, m), 3.72 (1H, s), 3.70 (1H, s), 3.56 (2H, m), 3.20 (1H, m), 3.13 (2H, m), 3.00 (1H, m), 2.85 (1H, m), 2.83 (3H, s), 2.77 (6H, s), 2.21 (2H, m), 2.12 (2H, m), 2.03-1.65 (12H, m) ppm.

Workup

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

Sources & evidence

ORD record
ord-fbcb8786a5024a84be48bd701ed74246
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

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