Hydrochloric Acid → HCID 86697072, compound

HRID 626775Notes

Reaction equation

HRID 626775 reaction equation
C([O:5][C:6](=[O:35])[NH:7][C:8]1[CH:13]=[C:12]([NH:14][C:15]2[C:20]3=[CH:21][N:22]([C:24]4[C:29]([C:30]#[N:31])=[CH:28][C:27]([NH2:32])=[CH:26][C:25]=4[Cl:33])[N:23]=[C:19]3[C:18]([F:34])=[CH:17][N:16]=2)[N:11]=[CH:10][N:9]=1)(C)(C)C.Cl>>[CH:6]([OH:35])=[O:5].[NH2:32][C:27]1[CH:26]=[C:25]([Cl:33])[C:24]([N:22]2[CH:21]=[C:20]3[C:15]([NH:14][C:12]4[CH:13]=[C:8]([NH2:7])[N:9]=[CH:10][N:11]=4)=[N:16][CH:17]=[C:18]([F:34])[C:19]3=[N:23]2)=[C:29]([CH:28]=1)[C:30]#[N:31]

Participants

3

Reactant 2

HCID 313Hydrochloric Acid2×HCID 86697073HCID 86697073, compound

Product 1

HCID 86697072HCID 86697072, compoundYield 59%

Procedure

A mixture of {6-[2-(4-amino-2-chloro-6-cyanophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridin-4-ylamino]-pyrimidin-4-yl}-bis-carbamic acid tert-butyl ester and {6-[2-(4-amino-2-chloro-6-cyanophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridin-4-ylamino]-pyrimidin-4-yl}-carbamic acid tert-butyl ester (66 mg, ˜0.12 mmol) in HCl (4 N in dioxane, 5.0 mL, 20 mmol) was stirred at room temperature overnight. Additional HCl (4 N in dioxane, 1.0 mL, 10 mmol) was added and the reaction mixture was heated at 40° C. for 7 hours. The resultant suspension was concentrated under reduced pressure and the residue was triturated with diethyl ether. The solid obtained was dried under vacuum and was purified by HPLC [gradient: 5 to 60% acetonitrile (0.1% formic acid) in water (0.1% formic acid)], to afford the title compound as a white solid (30 mg, 59% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.20 (s, 1H), 9.04 (d, J=2.4 Hz, 1H), 8.16 (d, J=1.1 Hz, 1H), 8.06 (d, J=3.0 Hz, 1H), 7.51 (d, J=1.1 Hz, 1H), 7.09 (d, J=2.5 Hz, 1H), 7.06 (d, J=2.5 Hz, 1H), 6.69 (s, 2H); 6.44 (s, 2H). LCMS (Method B): RT=2.70 min, m/z: 396 [M+H+].

Workup

  1. temperaturethe reaction mixture was heated at 40° C. for 7 hours
  2. concentrationThe resultant suspension was concentrated under reduced pressure
  3. customthe residue was triturated with diethyl ether
  4. customThe solid obtained
  5. customwas dried under vacuum
  6. customwas purified by HPLC [gradient: 5 to 60% acetonitrile (0.1% formic acid) in water (0.1% formic acid)]

Sources & evidence

ORD record
ord-7071c4f03ca74fafbc9dee193200929c
Source dataset
uspto-grants-2016_04
Patent number
US09309240B2

Reaction notes

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