Hydrochloric Acid → Hydrochloric Acid

HRID 449220Notes

Reaction equation

HRID 449220 reaction equation
[N:1]1([CH2:6][CH2:7][NH:8][C:9]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18]3[N:19]=[N:20][C:21]4[CH:27]=[C:26]([C:28]5[CH:33]=[C:32]([O:34]C)[CH:31]=[CH:30][C:29]=5[Cl:36])[CH:25]=[C:24]([CH3:37])[C:22]=4[N:23]=3)=[CH:13][N:12]=2)=[O:10])[CH2:5][CH2:4][CH2:3][CH2:2]1.B(Br)(Br)Br.[ClH:42].C(OCC)C>C(Cl)Cl.CO>[ClH:36].[N:1]1([CH2:6][CH2:7][NH:8][C:9]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18]3[N:19]=[N:20][C:21]4[CH:27]=[C:26]([C:28]5[CH:33]=[C:32]([OH:34])[CH:31]=[CH:30][C:29]=5[Cl:36])[CH:25]=[C:24]([CH3:37])[C:22]=4[N:23]=3)=[CH:13][N:12]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1.[ClH:42]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 25134Boron tribromideHCID 598377865-[7-(2-Chloro-5-methoxy-phenyl)-5-methyl-benzo[1,2,4]triazin-3-ylamino]-pyridine-2-carboxylic acid (2-pyrrolidin-1-yl-ethyl)-amide

Product 2

HCID 313Hydrochloric AcidHCID 1317307085-[7-(2-chloro-5-hydroxy-phenyl)-5-methyl-benzo[1,2,4]triazin-3-ylamino]-pyridine-2-carboxylic acid (2-pyrrolidin-1-yl-ethyl)-amide HCl salt

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

5-[7-(2-chloro-5-methoxy-phenyl)-5-methyl-benzo[1,2,4]triazin-3-ylamino]-pyridine-2-carboxylic acid (2-pyrrolidin-1-yl-ethyl)-amide (0.085 g, 0.164 mmol, 1 equiv) was diluted with 20 mL DCM and chilled to 0° C. using an ice bath. A 1.0 M solution of BBr3 in DCM (1 mL, 0.984 mmol, 6.0 equiv) was then added in one portion resulting in a dark reaction mixture. The reaction was allowed to come to ambient temperature and stirred for 6 hours, then quenched by carefully pouring onto a saturated solution of sodium bicarbonate followed by sonication for 5 minutes. The resulting solids were filtered off, dried, and dissolved in DCM (10 mL) and MeOH (20 mL) mixture and treated with 2.0 M solution of HCl in diethyl ether (0.16 mL, 0.317 mmol, 2 equiv). The solvents were evaporated leaving desired product as HCl salt in a form of a yellow solid (0.084 g, 95% yield). MS (ESI+): m/z=504.1, LC retention time: 2.23 min. 1H NMR (DMSO-d6): δ 1.86-1.88 (m, 2H), 1.99-2.02 (m, 2H), 2.70 (s, 3H), 3.01-3.05 (m, 2H), 3.33-3.37 (m, 2H), 6.90 (dd, J=8.7 Hz, J=2.9 Hz, 1H), 6.97 (d, J=2.9 Hz, 1H), 7.41 (d, J=8.8 Hz, 1H), 7.92-7.93 (m, 1H), 8.12 (d, J=8.7 Hz, 1H), 8.22 (d, J=1.5 Hz, 1H), 8.51 (dd, J=8.6 Hz, J=2.5 Hz, 1H), 9.06 (t, J=5.9 Hz, 1H), 9.43 (d, J=2.4 Hz, 1H), 10.17 (bs, 1H), 11.50 (s, 1H).

Workup

  1. customresulting in a dark reaction mixture
  2. customto come to ambient temperature
  3. customquenched
  4. additionby carefully pouring onto a saturated solution of sodium bicarbonate
  5. customfollowed by sonication for 5 minutes
  6. filtrationThe resulting solids were filtered off
  7. customdried
  8. dissolutiondissolved in DCM (10 mL)
  9. customThe solvents were evaporated

Sources & evidence

ORD record
ord-f0cf521847e44e7385b44a47333f001d
Source dataset
uspto-grants-2013_07
Patent number
US08481536B2

Reaction notes

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