Trifluoroacetic acid → Hydrochloric Acid

HRID 1050501Notes

Reaction equation

HRID 1050501 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][C:5]([NH:7][C@@H:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14]2[N:15]=[N:16][C:17]([C:35]([NH2:37])=[O:36])=[C:18]([NH:20][C:21]3[CH:26]=[CH:25][C:24]([C:27]([N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)=[O:28])=[CH:23][CH:22]=3)[N:19]=2)[CH2:9]1)=[O:6].[H-].[Na+].C(O)(C(F)(F)F)=O>CN(C=O)C.O>[N:29]1([C:27]([C:24]2[CH:25]=[CH:26][C:21]([NH:20][C:18]3[N:19]=[C:14]([N:10]4[CH2:11][CH2:12][CH2:13][C@@H:8]([N:7]5[CH2:2][CH2:3][CH2:4][C:5]5=[O:6])[CH2:9]4)[N:15]=[N:16][C:17]=3[C:35]([NH2:37])=[O:36])=[CH:22][CH:23]=2)=[O:28])[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.[ClH:1]

Participants

7

Reactant 3

HCID 6422Trifluoroacetic acidHCID 24758Sodium hydrideHCID 118114561HCID 118114561, compound

Product 2

HCID 313Hydrochloric AcidHCID 118114559HCID 118114559, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (R)-3-(3-aminopiperidin-1-yl)-5-(4-(morpholine-4-carbonyl)phenylamino)-1,2,4-triazine-6-carboxamide HCl salt (6) (90 mg, 0.19 mmol) in NMP (3 mL) was added DIEA (0.27 mL, 1.52 mmol) and then 3-bromopropanoyl chloride (108 mg, 0.58 mmol). The mixture was stirred at RT for 1 h and then at 60° C. for 1 h. The mixture was cooled to RT, diluted with EtOAc, washed with water and concentrated in vacuo to afford crude (R)-3-(3-(4-chlorobutanamido)piperidin-1-yl)-5-(4-(morpholine-4-carbonyl)phenylamino)-1,2,4-triazine-6-carboxamide. To a solution of (R)-3-(3-(4-chlorobutanamido)piperidin-1-yl)-5-(4-(morpholine-4-carbonyl)phenylamino)-1,2,4-triazine-6-carboxamide in DMF (3 mL) was added NaH (60% in mineral oil, 30 mg, 0.75 mmol). The mixture was stirred at RT for 1 h. The mixture was diluted with water, acidified with TFA, and subjected to reverse phase preparative HPLC to isolate the title compound (52) as HCl salt (31 mg). MS found for C24H30N8O4 as (M+H)+ 495.1, (M−H)− 493.2. UV: λ=275 nm.

Sources & evidence

ORD record
ord-5e7c81df39e94394ae59e8102b383962
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

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