Tert-Butylamine → N-tert-butyl-2-(1-methyl-6-(trifluoromethyl)-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

HRID 246662Notes

Reaction equation

HRID 246662 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]([F:14])([F:13])[F:12])[CH:9]=2)[C:4]([C:15]2[N:20]=[C:19]3[C:21]([C:24](O)=[O:25])=[CH:22][NH:23][C:18]3=[N:17][CH:16]=2)=[N:3]1.[CH3:27][C:28]([NH2:31])([CH3:30])[CH3:29].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C.O>[C:28]([NH:31][C:24]([C:21]1[C:19]2=[N:20][C:15]([C:4]3[C:5]4[C:10](=[CH:9][C:8]([C:11]([F:13])([F:12])[F:14])=[CH:7][CH:6]=4)[N:2]([CH3:1])[N:3]=3)=[CH:16][N:17]=[C:18]2[NH:23][CH:22]=1)=[O:25])([CH3:30])([CH3:29])[CH3:27]

Participants

8

Reactant 5

HCID 6385Tert-ButylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 712797642-(1-methyl-6-(trifluoromethyl)-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxylic acid

Product 1

HCID 71279529N-tert-butyl-2-(1-methyl-6-(trifluoromethyl)-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamideYield 21.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-(1-methyl-6-(trifluoromethyl)-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxylic acid (190 mg, 0.526 mmol), 2-methylpropan-2-amine (58 mg, 0.789 mmol), EDCI (301 mg, 1.578 mmol), HOBt (213 mg, 1.578 mmol) and DIPEA (204 mg, 1.578 mmol) in dry DMF (5 mL) was stirred for 16 hours at room temperature. Water (5 mL) was added, the formed precipitate was separated by filtration 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 are: 50% acetonitrile/50% water (0.1% trifluoroacetic acid V/V) initially, and then proceed to 90% acetonitrile/10% water (0.1% trifluoroacetic acid V/V) in a linear fashion after just 9 min.) to afford N-tert-butyl-2-(1-methyl-6-(trifluoromethyl)-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (47 mg, 21%) as a yellow solid. LCMS: (M+H)+=417; 1H NMR (300 MHz, DMSO): δ 12.82 (s, 1H), 9.08 (s, 1H), 8.63 (d, 1H, J=8.4 Hz), 8.38 (s, 1H), 8.30 (s, 1H), 7.89 (s, 1H), 7.49 (d, 1H, J=8.7 Hz), 4.28 (s, 3H), 1.22 (s, 9H).

Workup

  1. customthe formed precipitate was separated by filtration
  2. customthen purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm
  3. wait50% acetonitrile/50% water (0.1% trifluoroacetic acid V/V) initially, and then proceed to 90% acetonitrile/10% water (0.1% trifluoroacetic acid V/V) in a linear fashion after just 9 min.

Sources & evidence

ORD record
ord-e28d153b29d642169e0a8d970db74fa6
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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