Hydrochloric Acid → HCID 71134383, compound

HRID 1972933Notes

Reaction equation

HRID 1972933 reaction equation
[NH2:1][C:2]1[C:7]2=[C:8]([C:29]3[CH:30]=[CH:31][C:32]4[C:36]([CH:37]=3)=[N:35][N:34]([CH2:38][C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[CH:33]=4)[CH:9]=[C:10]([CH2:11][CH2:12][CH2:13][CH2:14][N:15]3[CH2:20][C@@H:19]4[CH2:21][C@H:16]3[CH2:17][N:18]4C(OC(C)(C)C)=O)[N:6]2[N:5]=[CH:4][N:3]=1.Cl>CO.O1CCOCC1>[CH2:38]([N:34]1[CH:33]=[C:32]2[C:36]([CH:37]=[C:29]([C:8]3[CH:9]=[C:10]([CH2:11][CH2:12][CH2:13][CH2:14][N:15]4[CH2:20][C@@H:19]5[CH2:21][C@H:16]4[CH2:17][NH:18]5)[N:6]4[C:7]=3[C:2]([NH2:1])=[N:3][CH:4]=[N:5]4)[CH:30]=[CH:31]2)=[N:35]1)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1

Participants

5

Reactant 2

HCID 313Hydrochloric Acid2×HCID 86761820HCID 86761820, compound

Product 1

HCID 71134383HCID 71134383, compoundYield 62%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of tert-butyl (1S,4S)-5-{-4-[4-amino-5-(2-benzyl-2H-indazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-7-yl]butyl}-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate in MeOH (1 mL) was added 4M HCl in dioxane (0.5 mL). The mixture was stirred at rt for 2 h. Additional 4M HCl in dioxane (0.5 mL) was added and the mixture continued to stir at rt for 16 h. The mixture was concentrated and the residue was partitioned between saturated, aqueous NaHCO3 (20 mL) and EtOAc (20 mL). The layers were separated and the organic phase was washed with brine, dried (Na2SO4) and concentrated. The residue was purified by preparative HPLC using a gradient elution from 15% to 50% acetonitrile in water to obtain 36 mg (62%) of the desired product. 1H NMR (400 MHz, DMSO-d6) δ 8.54 (s, 1 H), 7.88 (s, 1 H), 7.79 (d, 1 H), 7.57 (s, 1 H), 7.28-7.39 (m, 5 H), 7.13 (d, 1 H), 6.58 (s, 1 H), 5.64 (s, 2 H), 3.51 (s, 1 H), 3.25-3.47 (m, 2 H), 2.97 (d, 1 H), 2.87 (t, 2 H), 2.73 (dd, 1 H), 2.66 (dd, 2 H), 2.37-2.45 (m, 1 H), 2.33 (d, 1 H), 1.59-1.77 (m, 3 H), 1.35-1.52 (m, 3 H); ES-MS m/z 493.27 [M+H]+, HPLC RT (min) 1.89.

Workup

  1. stirringto stir at rt for 16 h
  2. concentrationThe mixture was concentrated
  3. customthe residue was partitioned between saturated, aqueous NaHCO3 (20 mL) and EtOAc (20 mL)
  4. customThe layers were separated
  5. washthe organic phase was washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customThe residue was purified by preparative HPLC
  9. washa gradient elution from 15% to 50% acetonitrile in water

Sources & evidence

ORD record
ord-7aa3a6b203c8443ba0147f74ddff02e0
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

Loading…