Dimethylformamide → 1-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carboxylic acid {(R)-2-carbamoyl-1-[5-(1H-pyrrolo[2,3-b]pyridin-3-yl)-thiophen-2-yl]-ethyl}-amide

HRID 1625471Notes

Reaction equation

HRID 1625471 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:35]=[CH:36][C:37]=1[F:38])[CH2:5][N:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]([NH:14][C@@H:15]([C:20]2[S:21][C:22]([C:25]3[C:33]4[C:28](=[N:29][CH:30]=[CH:31][CH:32]=4)[NH:27][CH:26]=3)=[CH:23][CH:24]=2)[CH2:16][C:17](O)=[O:18])=[O:13])[C:7]1=[O:34].C[N:40](C)C=O.[Cl-].[NH4+].C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1>>[C:17]([CH2:16][C@@H:15]([NH:14][C:12]([C:8]1[C:7](=[O:34])[N:6]([CH2:5][C:4]2[CH:35]=[CH:36][C:37]([F:38])=[C:2]([F:1])[CH:3]=2)[CH:11]=[CH:10][CH:9]=1)=[O:13])[C:20]1[S:21][C:22]([C:25]2[C:33]3[C:28](=[N:29][CH:30]=[CH:31][CH:32]=3)[NH:27][CH:26]=2)=[CH:23][CH:24]=1)(=[O:18])[NH2:40]

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59362416(R)-3-{[1-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carbonyl]-amino}-3-[5-(1H-pyrrolo[2,3-b]pyridin-3-yl)-thiophen-2-yl]-propionic acid

Product 1

HCID 593625851-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carboxylic acid {(R)-2-carbamoyl-1-[5-(1H-pyrrolo[2,3-b]pyridin-3-yl)-thiophen-2-yl]-ethyl}-amide

Procedure

(R)-3-{[1-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carbonyl]-amino}-3-[5-(1H-pyrrolo[2,3-b]pyridin-3-yl)-thiophen-2-yl]-propionic acid (0.026 g, 0.000049 mol;) was dissolved in N,N-Dimethylformamide (2 g, 0.03 mol;) and Ammonium chloride (0.0065 g, 0.00012 mol;), N,N-Diisopropylethylamine (42.4 uL, 0.000243 mol;), and N,N,N′,N′-Tetramethyl-O-(7-azabenzotriazol-1-yl)uronium Hexafluorophosphate (0.024 g, 0.000063 mol;) were added. After 2 hours the reaction was found to be complete by LC-MS 1.17 534.06. The crude reaction was directly injected onto the Gilson for purification to give the pure product. ES (+) MS m/e=534.06; NMR (400 MHz, DMSO-d6) δ ppm 2.78 (d, 2H, J=7 Hz), 5.22 (m, 2H), 5.66 (m, 1H), 6.66 (t, 1H, J=8 Hz), 6.99 (d, 1H, J=3 Hz), 7.14-7.21 (m, 3H), 7.38-7.49 (m, 3H), 7.79 (m, 1H), 8.2-8.25 (m, 2H), 8.29 (m, 1H), 8.4 (dd. 1H), 10.22 (d, 1H), 11.95 (s, 1H)

Workup

  1. customThe crude reaction
  2. customwas directly injected onto the Gilson for purification
  3. customto give the pure product

Sources & evidence

ORD record
ord-8488678588e743bda2eb877e17c4cedf
Source dataset
uspto-grants-2014_07
Patent number
US08778977B2

Reaction notes

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