4-Bromobutyryl chloride → HCID 118115754, compound

HRID 1050599Notes

Reaction equation

HRID 1050599 reaction equation
[CH:1]1([N:6]2[CH2:11][CH2:10][CH:9]([C:12]3[CH:17]=[CH:16][C:15]([NH:18][C:19]4[C:20]([C:38]([NH2:40])=[O:39])=[N:21][CH:22]=[C:23]([N:25]5[CH2:30][CH2:29][CH2:28][C@@H:27]([NH:31][C:32](N(CC)C)=[O:33])[CH2:26]5)[N:24]=4)=[CH:14][CH:13]=3)[CH2:8][CH2:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.[Br:50][CH2:51][CH2:52][CH2:53]C(Cl)=O>CN(C=O)C.CCOC(C)=O>[Br:50][CH2:51][CH2:52][CH2:53][C:32]([NH:31][C@@H:27]1[CH2:28][CH2:29][CH2:30][N:25]([C:23]2[N:24]=[C:19]([NH:18][C:15]3[CH:14]=[CH:13][C:12]([CH:9]4[CH2:10][CH2:11][N:6]([CH:1]5[CH2:5][CH2:4][CH2:3][CH2:2]5)[CH2:7][CH2:8]4)=[CH:17][CH:16]=3)[C:20]([C:38]([NH2:40])=[O:39])=[N:21][CH:22]=2)[CH2:26]1)=[O:33]

Participants

6

Reactant 3

HCID 702254-Bromobutyryl chlorideHCID 81531DiisopropylethylamineHCID 118114988HCID 118114988, compound

Product 1

HCID 118115754HCID 118115754, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

(R)-5-(3-Aminopiperidin-1-yl)-3-(4-(1-cyclopentylpiperidin-4-yl)phenylamino)pyrazine-2-carboxamide (436) (50 mg, 0.1 mmol) was dissolved in 4 mL DMF. To it were added DIEA (180 μL, 1.0 mmol) and then 4-bromobutyryl chloride (56 mg, 0.3 mmol). The mixture was stirred at RT for 1.5 hours, diluted with 60 mL EtOAc, washed with water ×3, dried, concentrated in vacuo to afford crude (R)-5-(3-(4-bromobutanamido)piperidin-1-yl)-3-(4-(1-cyclopentylpiperidin-4-yl)phenylamino)pyrazine-2-carboxamide (448). It was dissolved in 3 mL dry DMF and the solution was stirred at RT. To it was added NaH (60%, 30 mg), and the mixture was stirred for 1 hour. It was quenched with 0.5 mL TFA, and directly subjected to reverse phase preparative HPLC using 5 mM HCl (aq) and nest MeCN to isolate the title compound, (R)-3-(4-(1-cyclopentylpiperidin-4-yl)phenylamino)-5-(3-(2-oxopyrrolidin-1-yl)piperidin-1-yl)pyrazine-2-carboxamide (449), as HCl salt (7 mg). LC-MS (ESI): m/z (M+1) 532.6. UV: λ=267, 275, 305, 335, 373 nm.

Workup

  1. washwashed with water ×3
  2. customdried
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-230660e5b50846918fe6f6cf8d613709
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

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