Hydrochloric Acid → HCID 58529632, compound

HRID 1972936Notes

Reaction equation

HRID 1972936 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]([C:11]3[N:12]=[C:13]([CH:16]4[CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18][CH2:17]4)[S:14][CH:15]=3)[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]([C:11]4[N:12]=[C:13]([CH:16]5[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]5)[S:14][CH:15]=4)[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:40]=[CH:41][CH:42]=[CH:43][CH:44]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 58529406HCID 58529406, compound

Product 1

HCID 58529632HCID 58529632, compoundYield 7.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of tert-butyl 4-{4-[4-amino-5-(2-benzyl-2H-indazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-7-yl]-1,3-thiazol-2-yl}piperidine-1-carboxylate (81 mg, 0.13 mmol) in MeOH (600 μL) was added 4M HCl in dioxane (300 μL). The mixture was stirred at rt for 16 h. The mixture was concentrated and the residue was purified by preparative HPLC using a gradient elution from 15% to 45% acetonitrile in water followed by filtration through an acidic resin, washing with MeOH. The product was eluted with 2M NH3 in MeOH and the filtrate was concentrated to provide 5 mg (7%) of the desired product. 1H NMR (400 MHz, DMSO-d6) δ 8.80 (s, 1 H), 8.64 (s, 1 H), 8.59 (s, 1 H), 8.07 (d, 1 H), 7.98 (s, 1 H), 7.46-7.61 (m, 6H), 7.40 (dd, 1 H), 5.86 (s, 2 H), 3.51-3.69 (m, 3 H), 3.25 (t, 2 H), 2.39-2.50 (m, 2 H), 2.12 (q, 2 H); LC-MS [M+H]+=507.30, RT=2.69 min.

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was purified by preparative HPLC
  3. washa gradient elution from 15% to 45% acetonitrile in water
  4. filtrationfollowed by filtration through an acidic resin
  5. washwashing with MeOH
  6. washThe product was eluted with 2M NH3 in MeOH
  7. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-b016c598cd9248498edafce57e7766a1
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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