Dichloromethane → {6-[2-(4-Amino-2,6-dichlorophenyl)-7-fluorothiazolo[5,4-c]pyridin-4-ylamino]-pyrimidin-4-yl}-methanol dihydrochloride salt

HRID 2366321Notes

Reaction equation

HRID 2366321 reaction equation
C(OC(=O)[NH:7][C:8]1[CH:13]=[C:12]([Cl:14])[C:11]([C:15]2[S:16][C:17]3[C:18]([NH:25][C:26]4[CH:31]=[C:30]([CH2:32][OH:33])[N:29]=[CH:28][N:27]=4)=[N:19][CH:20]=[C:21]([F:24])[C:22]=3[N:23]=2)=[C:10]([Cl:34])[CH:9]=1)(C)(C)C.C(Cl)[Cl:37]>Cl>[ClH:14].[ClH:37].[NH2:7][C:8]1[CH:13]=[C:12]([Cl:14])[C:11]([C:15]2[S:16][C:17]3[C:18]([NH:25][C:26]4[N:27]=[CH:28][N:29]=[C:30]([CH2:32][OH:33])[CH:31]=4)=[N:19][CH:20]=[C:21]([F:24])[C:22]=3[N:23]=2)=[C:10]([Cl:34])[CH:9]=1

Participants

4

Reactant 2

HCID 6344DichloromethaneHCID 66801633{3,5-Dichloro-4-[7-fluoro-4-(6-hydroxymethylpyrimidin-4-ylamino)-thiazolo[5,4-c]pyridin-2-yl]phenyl}-carbamic acid tert-butyl ester

Product 1

HCID 66801844{6-[2-(4-Amino-2,6-dichlorophenyl)-7-fluorothiazolo[5,4-c]pyridin-4-ylamino]-pyrimidin-4-yl}-methanol dihydrochloride salt

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent2×

Conditions

Temperature
50 °C

Procedure

A mixture of {3,5-dichloro-4-[7-fluoro-4-(6-hydroxymethylpyrimidin-4-ylamino)-thiazolo[5,4-c]pyridin-2-yl]phenyl}-carbamic acid tert-butyl ester (102 mg, 0.19 mmol) in HCl (4 N in dioxane, 3 mL) under a nitrogen atmosphere was heated at 50° C. for 5 hours. After cooling to room temperature, the precipitate was collected by filtration and then purified by column chromatography on silica gel eluting with 0-5% MeOH in EtOAc. To the resultant solid obtained was added DCM (1 mL) followed by HCl (4 N in dioxane, 1 mL) and the resulting mixture was stirred at room temperature for 1 hour and then concentrated under reduced pressure to afford the title compound as an off white solid (50 mg, 91% yield). 1H NMR (300 MHz, DMSO-d6): δ 11.75 (br s, 1H), 8.89 (s, 1H), 8.57 (d, J=2.1 Hz, 1H), 7.70 (s, 1H), 6.78 (s, 2H), 4.61 (s, 2H). LCMS (Method C): RT=3.11 min, m/z: 437 [M+H+].

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationthe precipitate was collected by filtration
  3. custompurified by column chromatography on silica gel eluting with 0-5% MeOH in EtOAc
  4. customTo the resultant solid obtained
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-37de624af2254779981500b7470e727c
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

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