Diisopropylethylamine → HCID 58557125, compound

HRID 1969716Notes

Reaction equation

HRID 1969716 reaction equation
Br.[NH:2]1[CH2:7][CH2:6][CH2:5][C@@H:4]([C:8]2[N:12]3[C:13]4[CH:19]=[CH:18][NH:17][C:14]=4[N:15]=[CH:16][C:11]3=[N:10][CH:9]=2)[CH2:3]1.Br.N1CCC[C@H](C2N3C4C=CNC=4N=CC3=NC=2)C1.CCN(C(C)C)C(C)C.[F:48][C:49]1([F:56])[CH2:52][CH:51]([C:53](O)=[O:54])[CH2:50]1.CCN=C=NCCCN(C)C.Cl>CN(C=O)C>[CH:19]1[C:13]2[N:12]3[C:8]([C@@H:4]4[CH2:5][CH2:6][CH2:7][N:2]([C:53]([CH:51]5[CH2:52][C:49]([F:56])([F:48])[CH2:50]5)=[O:54])[CH2:3]4)=[CH:9][N:10]=[C:11]3[CH:16]=[N:15][C:14]=2[NH:17][CH:18]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 137777893,3-Difluorocyclobutane-1-carboxylic acidHCID 67216753HCID 67216753, compoundHCID 67999295HCID 67999295, compound

Product 1

HCID 58557125HCID 58557125, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of (R)-8-(piperidin-3-yl)-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazine hydrobromide and (S)-8-(piperidin-3-yl)-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazine hydrobromide [er=80:20](0.30 g, 0.93 mmol), DIEA (0.52 mL, 3.0 mmol) and 3,3-difluorocyclobutanecarboxylic acid (0.35 g, 3.1 mmol, Waterstone) in DMF (4 mL) was added EDC•HCl (0.21 g, 1.1 mmol). The reaction was stirred at about 25° C. for about 4 h. The reaction was partitioned with aqueous Na2CO3 (2 M, 25 mL) and DCM (25 mL). The organic layer was separated, dried over anhydrous Na2SO4, filtered, and concd in vacuo. The resulting residue was purified on silica gel (12 g) using 0-5% MeOH in DCM followed by purification using General Procedure AA (Table 2, Method 23, Rt=16.4 min, or =positive) to give (R)-(3-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)piperidin-1-yl)(3,3-difluorocyclobutyl)-methanone (0.10 g, 30%): LC/MS (Table 1, Method b) Rt=1.85 min; MS m/z: 360 (M+H)+.

Workup

  1. customThe reaction was partitioned with aqueous Na2CO3 (2 M, 25 mL) and DCM (25 mL)
  2. customThe organic layer was separated
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. customThe resulting residue was purified on silica gel (12 g)
  6. customfollowed by purification

Sources & evidence

ORD record
ord-c842baa920a7431393701a55dd4bbaff
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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