Diisopropylethylamine → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-N-(1-methylcyclopentyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246583Notes

Reaction equation

HRID 246583 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21](O)=[O:22])=[CH:19][NH:18][C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.Cl.[CH3:25][C:26]1([NH2:31])[CH2:30][CH2:29][CH2:28][CH2:27]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21]([NH:31][C:26]5([CH3:25])[CH2:30][CH2:29][CH2:28][CH2:27]5)=[O:22])=[CH:19][NH:18][C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 115064601-methylcyclopentan-1-amine HydrochlorideHCID 712796392-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 1

HCID 712798762-(6-fluoro-1-methyl-1H-indazol-3-yl)-N-(1-methylcyclopentyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 22.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (62 mg, 0.20 mmol), 1-methylcyclopentanamine hydrochloride (35 mg, 0.26 mmol), HATU (98 mmol, 0.26 mmol) and DIEA (42 mg, 0.33 mmol) in 6 mL of DMF was stirred at room temperature for 16 hours. The solvent was evaporated at 70° C. under reduced pressure to give a crude product, which was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; the gradient conditions were: 55% acetonitrile/45% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 80% acetonitrile/20% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.) to give 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-N-(1-methylcyclopentyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (18 mg, 22.9%) as an off-white solid. MS: (M+H)+=393; 1H NMR (300 MHz, DMSO): δ 12.84 (s, 1H), 9.09 (s, 1H), 8.49-8.44 (m, 1H), 8.41 (s, 1H), 8.01 (s, 1H), 7.72 (d, 1H, J=7.8 Hz), 7.17 (t, 1H, J=8.1 Hz), 4.17 (s, 3H), 2.19 (brs, 2H), 1.79-1.76 (m, 6H), 1.57 (s, 3H).

Workup

  1. customThe solvent was evaporated at 70° C. under reduced pressure
  2. customto give a crude product, which
  3. customwas purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm

Sources & evidence

ORD record
ord-8e86a35293af43feb6f5114b87057e92
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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