Morpholine → HCID 118114597, compound

HRID 1050497Notes

Reaction equation

HRID 1050497 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[N:16]=[N:17][C:18]([C:31](=[O:33])[NH2:32])=[C:19]([NH:21][C:22]3[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][CH:23]=3)[N:20]=2)[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1.CCN(C(C)C)C(C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[C:31]([C:18]1[N:17]=[N:16][C:15]([N:11]2[CH2:12][CH2:13][CH2:14][C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:2])[CH3:4])[CH2:10]2)=[N:20][C:19]=1[NH:21][C:22]1[CH:23]=[CH:24][C:25]([C:26]([N:34]2[CH2:39][CH2:38][O:37][CH2:36][CH2:35]2)=[O:27])=[CH:29][CH:30]=1)(=[O:33])[NH2:32]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 118115209HCID 118115209, compound

Product 1

HCID 118114597HCID 118114597, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Compound 5 (90 mg, 0.20 mmol) was mixed with morpholine (53 μL, 0.60 mmol) in DMF (5 mL). To the mixture were added DIEA (105 μL, 0.60 mmol) and PyBOP (312 mg, 0.60 mmol). The mixture was stirred for 5 min, diluted with 100 mL EtOAc, washed with brine ×2, dried, and concentrated in vacuo. The residue was subjected to flash column chromatography with 50 to 100% EtOAc in hexane to isolate (R)-tert-butyl 1-(6-carbamoyl-5-(4-(morpholine-4-carbonyl)phenylamino)-1,2,4-triazin-3-yl)piperidin-3-ylcarbamate in quantitative yield. (R)-tert-butyl 1-(6-carbamoyl-5-(4-(morpholine-4-carbonyl)phenylamino)-1,2,4-triazin-3-yl)piperidin-3-ylcarbamate was treated with DCM (10 mL) and TFA (3 mL) for 1 h at RT. The mixture was concentrated in vacuo to dryness. The residue was subjected to reverse phase prep HPLC to isolate the (R)-3-(3-aminopiperidin-1-yl)-5-(4-(morpholine-4-carbonyl)phenylamino)-1,2,4-triazine-6-carboxamide (6) as HCl salt. MS found for C20H26N8O3 as (M+H)+ 427.1, (M−H)− 425.2. UV: λ=270 nm.

Workup

  1. washwashed with brine ×2
  2. customdried
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-86f84b95e69240ffb0c07f1d04b16899
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

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