Hydrochloric Acid → HCID 86677934, compound

HRID 246010Notes

Reaction equation

HRID 246010 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C@H:7]([NH:9][C:10]([C:12]1[C:20]2[C:15](=[N:16][CH:17]=[C:18]([C:21]3[C:29]4[C:24](=[CH:25][C:26]([F:30])=[CH:27][CH:28]=4)[N:23]([CH3:31])[N:22]=3)[N:19]=2)[N:14](COCC[Si](C)(C)C)[CH:13]=1)=[O:11])[CH3:8].C(O)(C(F)(F)F)=O.C(N)CN.[ClH:51].CO>C(Cl)Cl>[ClH:51].[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C@H:7]([NH:9][C:10]([C:12]1[C:20]2[C:15](=[N:16][CH:17]=[C:18]([C:21]3[C:29]4[C:24](=[CH:25][C:26]([F:30])=[CH:27][CH:28]=4)[N:23]([CH3:31])[N:22]=3)[N:19]=2)[NH:14][CH:13]=1)=[O:11])[CH3:8]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 887MethanolHCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 71286094HCID 71286094, compound

Product 1

HCID 86677934HCID 86677934, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-pyridin-2-yl-ethyl)-amide (117 mg, 0.21 mmol) in CH2Cl2 (2 mL) was added TFA (1 mL, 13.0 mmol). The bright yellow-orange reaction mixture was stirred at room temperature for 3 h then concentrated. The residue was redissolved in CH2Cl2 (2 mL) and ethylene diamine (0.5 mL, 7.50 mmol) was added. The reaction mixture was stirred for 1 h then chromatographed directly with 50% to 100% EtOAc/hexanes to 5% MeOH/EtOAc. The white solid thus isolated was triturated with EtOAc then suspended in CH2Cl2 and MeOH (1:1, 6 mL). 1.0M HCl in MeOH (2 eq) was added which caused complete dissolution. The solution was concentrated and dried under high vacuum to afford 67 mg (69%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-pyridin-2-yl-ethyl)-amide hydrochloride as a light yellow solid. MS (M+H)+=416; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.93 (d, J=2.6 Hz, 1H), 9.13 (s, 1H), 8.83 (d, J=7.6 Hz, 1H), 8.73 (dd, J=8.9, 5.5 Hz, 1H), 8.59 (d, J=4.9 Hz, 1H), 8.44 (d, J=3.0 Hz, 1H), 8.07 (br. s., 1H), 7.76 (d, J=7.9 Hz, 1H), 7.68 (dd, J=9.6, 2.1 Hz, 1H), 7.53 (br. s., 1H), 7.05 (td, J=9.1, 1.9 Hz, 1H), 5.44 (quin, J=7.0 Hz, 1H), 4.15 (s, 3H), 1.67 (d, J=6.8 Hz, 3H).

Workup

  1. concentrationthen concentrated
  2. dissolutionThe residue was redissolved in CH2Cl2 (2 mL)
  3. stirringThe reaction mixture was stirred for 1 h
  4. customthen chromatographed directly with 50% to 100% EtOAc/hexanes to 5% MeOH/EtOAc
  5. customThe white solid thus isolated
  6. customwas triturated with EtOAc
  7. dissolutiondissolution
  8. concentrationThe solution was concentrated
  9. customdried under high vacuum

Sources & evidence

ORD record
ord-2742e71f3d264d3fb088da0c1636ad91
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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