Hydrochloric Acid → HCID 58465021, compound

HRID 2089348Notes

Reaction equation

HRID 2089348 reaction equation
C(OC(=O)[NH:10][C@@H:11]1[CH2:17][CH2:16][CH2:15][N:14]([C:18]2[N:19]([CH3:49])[N:20]=[CH:21][C:22]=2[NH:23][C:24]([C:26]2[N:27]=[C:28]([C:39]3[C:44]([F:45])=[CH:43][C:42]([O:46][CH3:47])=[CH:41][C:40]=3[F:48])[S:29][C:30]=2[NH:31]C(OC(C)(C)C)=O)=[O:25])[CH2:13][CH2:12]1)C1C=CC=CC=1.Cl>>[NH2:31][C:30]1[S:29][C:28]([C:39]2[C:40]([F:48])=[CH:41][C:42]([O:46][CH3:47])=[CH:43][C:44]=2[F:45])=[N:27][C:26]=1[C:24]([NH:23][C:22]1[CH:21]=[N:20][N:19]([CH3:49])[C:18]=1[N:14]1[CH2:15][CH2:16][CH2:17][C@@H:11]([NH2:10])[CH2:12][CH2:13]1)=[O:25]

Participants

3

Reactant 2

HCID 313Hydrochloric AcidHCID 58464762HCID 58464762, compound

Product 1

HCID 58465021HCID 58465021, compoundYield 96.3%

Conditions

Temperature
100 °C

Procedure

A heterogeneous mixture of [(R)-1-(4-{[5-tert-butoxycarbonylamino-2-(2,6-difluoro-4-methoxyphenyl)-thiazole-4-carbonyl]-amino}-2-methyl-2H-pyrazol-3-yl)-perhydro-azepin-4-yl]-carbamic acid benzyl ester (14.5 mg, 0.02 mmol) and 2M aq. HCl (5 mL) was stirred at 100° C. under N2 for 4 h. The resultant homogeneous reaction was cooled to RT and the water solvent was removed using toluene azeotrope. The crude was redissolved in 9:1 v/v DMF:MeOH (1 mL) and purified via reverse phase HPLC to afford 202 (9.2 mg, 94.3%) as a white solid. 1H NMR (400 MHz, DMSO) δ 8.75 (broad s, 1H), 8.46 (s, 1H), 7.53 (s, 1H), 7.42 (s, 2H), 6.95 (s, 1H), 6.92 (s, 1H), 3.85 (s, 3H), 3.64 (s, 3H), 3.20-3.04 (m, 6H), 1.95-1.77 (m, 3H), 1.68-1.52 (m, 3H); MS (ESI) m/z: 479.1 [M+H]+

Workup

  1. customThe resultant homogeneous reaction
  2. temperaturewas cooled to RT
  3. customthe water solvent was removed
  4. dissolutionThe crude was redissolved in 9:1 v/v DMF
  5. customMeOH (1 mL) and purified via reverse phase HPLC

Sources & evidence

ORD record
ord-3dac08a2f0f84c5b92000ec82eb2b649
Source dataset
uspto-grants-2013_05
Patent number
US08436001B2

Reaction notes

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