4-Methylmorpholine → (S)-1-(4-fluorophenyl)-N-(1-(8-methylpyrrolo[1,2-a]pyrazin-1-yl)pyrrolidin-3-yl)-1H-pyrazole-3-carboxamide

HRID 1755260Notes

Reaction equation

HRID 1755260 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:12]=[CH:11][C:10]([C:13]([OH:15])=O)=[N:9]2)=[CH:4][CH:3]=1.[CH3:16][C:17]1[CH:18]=[CH:19][N:20]2[CH:25]=[CH:24][N:23]=[C:22]([N:26]3[CH2:30][CH2:29][C@H:28]([NH2:31])[CH2:27]3)[C:21]=12.CCCP(=O)=O.CN1CCOCC1>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH:12]=[CH:11][C:10]([C:13]([NH:31][C@H:28]3[CH2:29][CH2:30][N:26]([C:22]4[C:21]5[N:20]([CH:19]=[CH:18][C:17]=5[CH3:16])[CH:25]=[CH:24][N:23]=4)[CH2:27]3)=[O:15])=[N:9]2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 16167369Propylphosphoric anhydrideHCID 289740501-(4-fluorophenyl)-1H-pyrazole-3-carboxylic acidHCID 86720522(S)-1-(8-methylpyrrolo[1,2-a]pyrazin-1-yl)pyrrolidin-3-amine

Product 1

HCID 75202553(S)-1-(4-fluorophenyl)-N-(1-(8-methylpyrrolo[1,2-a]pyrazin-1-yl)pyrrolidin-3-yl)-1H-pyrazole-3-carboxamideYield 57%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-(4-fluorophenyl)-1H-pyrazole-3-carboxylic acid (0.04 g, 0.19 mmol, 1.5 eq) in 1 mL of DCM was added (S)-1-(8-methylpyrrolo[1,2-a]pyrazin-1-yl)pyrrolidin-3-amine (0.036 g, 0.13 mmol, 1 eq), propylphosphonic anhydride (0.3 mL, 0.47 mmol, 2.5 eq), and N-methylmorpholine (0.15 mL, 1.36 mmol, 10.5 eq). The reaction mixture was stirred at room temperature for 1 h then quenched with H2O and extracted with ethyl acetate. The combined organic layers were concentrated and purified by HPLC to afford (S)-1-(4-fluorophenyl)-N-(1-(8-methylpyrrolo[1,2-a]pyrazin-1-yl)pyrrolidin-3-yl)-1H-pyrazole-3-carboxamide (0.030 g, 0.074 mmol, 57%). 1H NMR (400 MHz, CDCCl3) δ 7.91 (d, J=7.3 Hz, 1 H), 7.82 (s, 1 H), 7.68 (dd, J=4.4, 8.8 Hz, 2 H), 7.33 (d, J=4.8 Hz, 1 H), 7.19 (t, J=8.8 Hz, 3 H), 7.00 (m, 2 H), 6.50 (s, 1 H), 4.75 (s, 1 H), 3.90-3.56 (m, 4 H), 2.57 (s, 3 H), 2.42-2.38 (m, 1 H), 2.02-1.80 (m, 1 H); MS: (ES) m/z calculated for C22H21FN6O[M+H]+ 405.2, found 405.

Workup

  1. customthen quenched with H2O
  2. extractionextracted with ethyl acetate
  3. concentrationThe combined organic layers were concentrated
  4. custompurified by HPLC

Sources & evidence

ORD record
ord-f479d539b17d4f12845f9619fe91c732
Source dataset
uspto-grants-2015_10
Patent number
US09169261B2

Reaction notes

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