1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2-(6-chloro-1-methyl-1H-indazol-3-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246589

Reaction equation

HRID 246589 reaction equation
[Cl: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.[F:24][C:25]([F:31])([F:30])[C:26]([CH3:29])([NH2:28])[CH3:27].CCN=C=NCCCN(C)C.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(C1C=CN=CC=1)C.CN(C=O)C>[Cl: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:28][C:26]([CH3:29])([CH3:27])[C:25]([F:31])([F:30])[F:24])=[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

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 112751881,1,1-Trifluoro-2-methylpropan-2-amineHCID 71280096HCID 71280096, compound

Product 1

HCID 712797002-(6-chloro-1-methyl-1H-indazol-3-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 16%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (0.07 g, 0.3 mmol), 1,1,1-trifluoro-2-methylpropan-2-amine (0.05 g, 0.39 mmol), EDCI (0.057 g, 0.3 mmol), DMAP (0.037 g, 0.3 mmol), HATU (0.114 g, 0.3 mmol) and DIPEA (0.163 g, 1.26 mmol) in 10 mL of DMF were stirred at room temperature overnight. The solvent was removed under reduced pressure at 70° C. The residue was triturated with water and then 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-chloro-1-methyl-1H-indazol-3-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (0.015 g, 16%) as a white solid. MS: (M+H)+=437; 1H NMR (300 MHz, DMSO): δ 13.03 (s, 1H), 9.10 (s, 1H), 8.53-8.82 (m, 1H), 8.42 (d, 1H, J=8.4 Hz), 8.14 (s, 1H), 8.39 (s, 1H), 7.28 (d, 1H, J=8.7 Hz), 4.20 (s, 3H), 1.77 (s, 6H).

Workup

  1. customThe solvent was removed under reduced pressure at 70° C
  2. customThe residue was triturated with water
  3. custompurified by preparative-HPLC (Gemini 5u C18 150×21.2 mm
  4. wait55% 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.

Sources & evidence

ORD record
ord-80b06cc6976c44daa10c3fd64ff836d7
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Linked notes

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