Hydrochloric Acid → (S)-2-{[5-(2,4-Difluorophenoxy)-1-isobutyl-1H-indazole-6-carbonyl]-amino}-4-dimethylaminobutyric acid

HRID 909208Notes

Reaction equation

HRID 909208 reaction equation
C[Si](C)(C)[O-].[K+].C[O:8][C:9](=[O:41])[C@@H:10]([NH:16][C:17]([C:19]1[CH:27]=[C:26]2[C:22]([CH:23]=[N:24][N:25]2[CH2:28][CH:29]([CH3:31])[CH3:30])=[CH:21][C:20]=1[O:32][C:33]1[CH:38]=[CH:37][C:36]([F:39])=[CH:35][C:34]=1[F:40])=[O:18])[CH2:11][CH2:12][N:13]([CH3:15])[CH3:14].Cl>C1COCC1>[F:40][C:34]1[CH:35]=[C:36]([F:39])[CH:37]=[CH:38][C:33]=1[O:32][C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][C:19]=1[C:17]([NH:16][C@@H:10]([CH2:11][CH2:12][N:13]([CH3:14])[CH3:15])[C:9]([OH:41])=[O:8])=[O:18])[N:25]([CH2:28][CH:29]([CH3:31])[CH3:30])[N:24]=[CH:23]2

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 23668039Potassium trimethylsilanolateHCID 57639703HCID 57639703, compound

Product 1

HCID 42611138(S)-2-{[5-(2,4-Difluorophenoxy)-1-isobutyl-1H-indazole-6-carbonyl]-amino}-4-dimethylaminobutyric acidYield 68.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Potassium trimethylsilanolate (1.77 g, 13.8 mmol) was added to a solution of (S)-2-{[5-(2,4-difluorophenoxy)-1-isobutyl-1H-indazole-6-carbonyl]-amino}-4-dimethylaminobutyric acid methyl ester (3.36 g, 6.88 mmol) in THF (5 mL). The reaction mixture was stirred at room temperature for 4 hours. HCl (17 mL of 4M in dioxane) was added to the mixture before it was concentrated under reduced pressure. The residue was suspended in dichloromethane and filtered. The filtrate was concentrated under reduced pressure to afford 2.23 g of product (68% yield). MS (ESI+) m/z 475 (M+1) detected; 1H NMR (400 mHz, DMSO-D6) δ 8.81 (d, 1H), 8.02 (s, 1H), 7.99 (s, 1H), 7.48 (m, 1H), 7.25 (m, 1H), 7.22 (s, 1H), 7.11 (m, 1H), 4.50 (m, 1H), 4.28 (d, 2H), 3.17 (m, 1H), 3.04 (m, 1H), 2.70 (s, 6H), 2.25 (m, 2H), 2.13 (m, 1H), 0.87 (d, 6H).

Workup

  1. concentrationwas concentrated under reduced pressure
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-c984a5ef4afa45b1ac99364c9a5faecf
Source dataset
uspto-grants-2011_09
Patent number
US08017641B2

Reaction notes

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