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Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → (R)-ethyl 4-(biphenyl-4-yl)-3-(6-(methylsulfonamido)nicotinamido)butanoate

HRID 70839
Notes
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Reaction equation

HRID 70839 reaction equation
Cl.[NH2:2][C@H:3]([CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19](Cl)[CH:18]=2)=[CH:13][CH:12]=1)[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].[CH3:24][S:25]([NH:28][C:29]1[CH:37]=[CH:36][C:32]([C:33](O)=[O:34])=[CH:31][N:30]=1)(=[O:27])=[O:26].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.CN(C=O)C>[C:14]1([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:15]=[CH:16][C:11]([CH2:10][C@@H:3]([NH:2][C:33](=[O:34])[C:32]2[CH:36]=[CH:37][C:29]([NH:28][S:25]([CH3:24])(=[O:27])=[O:26])=[N:30][CH:31]=2)[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6])=[CH:12][CH:13]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 587956276-Methanesulfonamidopyridine-3-carboxylic acidHCID 86648190(R)-ethyl 3-amino-4-(3'-chlorobiphenyl-4-yl)butanoate hydrochloride

Product 1

HCID 59607673(R)-ethyl 4-(biphenyl-4-yl)-3-(6-(methylsulfonamido)nicotinamido)butanoate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-ethyl 3-amino-4-(3′-chlorobiphenyl-4-yl)butanoate hydrochloride (103 mg, 0.32 mmol) and 6-(methylsulfonamido)nicotinic acid, intermediate 15, (84 mg, 0.39 mmol) in CH2Cl2 (2 mL) and DMF (2 mL) is added TEA (0.18 mL, 1.29 mmol) and HATU (159 mg, 0.42 mmol) at room temperature. The crude is stirred at room temperature for 2 hrs. The crude is quenched with saturated NaHCO3, diluted in EtOAc. The organic layer is washed with six times with water, brine, dried over MgSO4, filtered, and concentrated. The crude is purified via RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN) to give (R)-ethyl 4-(biphenyl-4-yl)-3-(6-(methylsulfonamido)nicotinamido)butanoate as a white solid (4.1 mg). HPLC retention time=1.61 minutes (condition A); MS (m+1)=482.3. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J=7.2 Hz, 3 H), 2.56 (t, J=4.8 Hz, 2 H), 2.84-2.92 (m, 1 H), 3.05 (dd, J=13.6, 6.1 Hz, 1 H), 3.16 (s, 3 H), 4.08-4.18 (m, 2 H), 4.57-4.71 (m, 1 H), 7.03 (d, J=8.3 Hz, 1 H), 7.10 (d, J=8.3 Hz, 1 H), 7.22 (d, J=8.3 Hz, 2 H), 7.26-7.31 (m, 1 H), 7.33-7.40 (m, 2 H), 7.44-7.54 (m, 5 H), 7.98 (dd, J=8.8, 2.3 Hz, 1 H), 8.52 (s, 1 H).

Workup

  1. customThe crude is quenched with saturated NaHCO3
  2. additiondiluted in EtOAc
  3. washThe organic layer is washed with six times with water, brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude is purified via RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN)

Sources & evidence

ORD record
ord-586ea8db0ef747b19c99357ad0fe2b2b
Source dataset
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08822534B2

Reaction notes

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