Hydrochloric Acid → HCID 66829935, compound

HRID 1040972Notes

Reaction equation

HRID 1040972 reaction equation
[OH-].[Li+].FC(F)(F)C(O)=O.C([O:12][C:13]([CH:15]1[CH2:20][CH2:19][N:18]([C:21]2[CH:26]=[CH:25][C:24]([NH:27][C:28]3[C:33]([Cl:34])=[CH:32][N:31]=[C:30]([NH:35][C:36]4[CH:37]=[CH:38][C:39]5[NH:45][C:44](=[O:46])[CH2:43][CH2:42][C:41]([CH3:48])([CH3:47])[C:40]=5[CH:49]=4)[N:29]=3)=[C:23]([N:50]3[CH:54]=[CH:53][CH:52]=[N:51]3)[CH:22]=2)[CH2:17][CH2:16]1)=[O:14])C.CO.Cl>O>[Cl:34][C:33]1[C:28]([NH:27][C:24]2[CH:25]=[CH:26][C:21]([N:18]3[CH2:19][CH2:20][CH:15]([C:13]([OH:14])=[O:12])[CH2:16][CH2:17]3)=[CH:22][C:23]=2[N:50]2[CH:54]=[CH:53][CH:52]=[N:51]2)=[N:29][C:30]([NH:35][C:36]2[CH:37]=[CH:38][C:39]3[NH:45][C:44](=[O:46])[CH2:43][CH2:42][C:41]([CH3:47])([CH3:48])[C:40]=3[CH:49]=2)=[N:31][CH:32]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 3939Lithium HydroxideHCID 86633900HCID 86633900, compound

Product 1

HCID 66829935HCID 66829935, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a room temperature solution of Lithium hydroxide (53 mg, 2.2 mmol) in Water (3 mL), was added 1-{4-[5-Chloro-2-(5,5-dimethyl-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-7-ylamino)-pyrimidin-4-ylamino]-3-pyrazol-1-yl-phenyl}-piperidine-4-carboxylic acid ethyl ester; compound with trifluoro-acetic acid (47 mg, 0.063 mmol) followed by Methanol (12 mL). After 72 hours 1 N HCl (2 mL) was added to the reaction to neutralize the base, then the mixture was concentrated under reduced pressure. The residue was purified by preparative reverse phase HPLC to yield the desired 1-{4-[5-Chloro-2-(5,5-dimethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-3-pyrazol-1-yl-phenyl}-piperidine-4-carboxylic acid as a lyophylate (20%); 1H NMR (400 MHz, DMSO-d6) δ 9.81 (s, 1H), 9.39 (s, 1H), 9.32 (s, 1H), 8.26 (s, 1H), 8.09 (s, 1H), 7.97 (m, 1H), 7.83 (s, 1H), 7.57 (d, J=7.07 Hz, 1H), 7.42 (s, 1H), 7.12 (s, 1H), 6.97 (d, J=9.86 Hz, 1H), 6.79 (d, J=8.34 Hz, 1H), 6.54 (s, 1H), 3.75 (m, 2H), 2.8 (m, 2H), 2.6 (m, 1H), 2.15 (m, 2H), 1.99 (m, 4H), 1.70 (m, 2H), 1.2 (s, 6H); MS (m/e) 601.56 (M+H).

Workup

  1. concentrationthe mixture was concentrated under reduced pressure
  2. customThe residue was purified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-e5fb15d55a484f289039552c85ad6829
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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