Hydrochloric Acid → HCID 178478933, compound

HRID 246619Notes

Reaction equation

HRID 246619 reaction equation
[F:1][CH:2]([F:40])[O:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH3:13])[N:8]=[C:7]2[C:14]1[N:15]=[C:16]2[C:22]([C:23]([NH:25][C@@H:26]3[CH2:31][CH2:30][C@H:29]([NH:32]C(=O)OC(C)(C)C)[CH2:28][CH2:27]3)=[O:24])=[CH:21][NH:20][C:17]2=[N:18][CH:19]=1.[ClH:41]>O1CCOCC1>[ClH:41].[NH2:32][C@@H:29]1[CH2:28][CH2:27][C@H:26]([NH:25][C:23]([C:22]2[C:16]3=[N:15][C:14]([C:7]4[C:6]5[C:10](=[CH:11][CH:12]=[C:4]([O:3][CH:2]([F:1])[F:40])[CH:5]=5)[N:9]([CH3:13])[N:8]=4)=[CH:19][N:18]=[C:17]3[NH:20][CH:21]=2)=[O:24])[CH2:31][CH2:30]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 178481759HCID 178481759, compound

Product 1

HCID 178478933HCID 178478933, compoundYield 29.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
25 °C

Procedure

tert-Butyl cis-4-(2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)cyclohexylcarbamate (54 mg, 0.1 mmol) in 3 mL of 1,4-dioxane was added 10 mL of concentrated HCl. The reaction mixture was stirred overnight at 25° C. After evaporation under the reduced pressure, the residue 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 are: 40% acetonitrile/60% water (0.1% trifluoroacetic acid V/V) initially, and then proceed to 50% acetonitrile/50% water (0.1% trifluoroacetic acid V/V) in a linear fashion after just 9 min). After concentration, the crude solid was treated with 1N HCl (2 mL), the mixture was stirred for 10 min then evaporated and dried to afford N-(cis-4-aminocyclohexyl)-2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide hydrochloride (13 mg, 29.5%) as yellow solid. LCMS: (M+H)+=456; 1H NMR (300 MHz, CD3OD): δ 8.96 (s, 1H), 8.22 (s, 1H), 8.01 (d, 1H, J=2.1 Hz), 7.56 (d, 1H, J=9.0 Hz), 7.26 (dd, 1H, J1=9.0 Hz, J2=2.4 Hz), 6.76 (t, 1H, J=74.1 Hz), 4.16-4.14 (m, 1H), 4.11 (s, 3H), 3.17-3.15 (m, 1H), 2.15-2.11 (m, 2H), 1.91-1.78 (m, 4H), 1.60-1.48 (m, 2H).

Workup

  1. customAfter evaporation under the reduced pressure
  2. customthe residue was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm
  3. wait40% acetonitrile/60% water (0.1% trifluoroacetic acid V/V) initially, and then proceed to 50% acetonitrile/50% water (0.1% trifluoroacetic acid V/V) in a linear fashion after just 9 min
  4. concentrationAfter concentration
  5. additionthe crude solid was treated with 1N HCl (2 mL)
  6. stirringthe mixture was stirred for 10 min
  7. customthen evaporated
  8. customdried

Sources & evidence

ORD record
ord-f67a042efe8743b5a7f84b580a1db2ae
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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