Diisopropylethylamine → HCID 89722227, compound

HRID 57718Notes

Reaction equation

HRID 57718 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:6]([NH2:10])[CH:7]=[N:8][CH:9]=1)=[O:4].[CH2:11]([N:18]1[CH2:22][CH:21]([C:23]([F:26])([F:25])[F:24])[CH:20]([C:27](O)=[O:28])[CH2:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[N:6]([NH:10][C:27]([CH:20]2[CH:21]([C:23]([F:25])([F:24])[F:26])[CH2:22][N:18]([CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH2:19]2)=[O:28])[CH:7]=[N:8][CH:9]=1)=[O:4]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11665425Methyl 1-amino-1H-imidazole-5-carboxylateHCID 196913861-Benzyl-4-(trifluoromethyl)pyrrolidine-3-carboxylic acid

Product 1

HCID 89722227HCID 89722227, compoundYield 85.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of compound 2 (2.0 g, 14.1 mmol), 1-Benzyl-4-trifluoromethyl-pyrrolidine-3-carboxylic acid (4.06 g, 14.9 mmol) and DIEA (10 mL, 42.5 mmol) in DMF (30 mL) was added HATU (8.1 g, 21.2 mmol). The resulting reaction mixture was stirred at r.t. overnight. The reaction was monitored by LC-MS. The reaction was quenched with water (100 mL) when it was complete. The aqueous solution was extracted with EtOAc (80 mL×3). The combined organic phase was washed with brine and concentrated to afford the crude product. The residue was purified by silica gel column (eluted with PE/EA=5:1 to 1:2) to afford compound 13 (4.8 g, 85.6% yield) as white oil. LC-MS: m/z 397 [M+1]+. 1H NMR (400 MHz, CDCl3): δ 8.00 (br. s, 1H), 7.70 (s, 1H), 7.65 (s, 1H), 7.34˜7.28 (m, 5H), 3.81 (s, 3H), 3.78˜3.72 (m, 2H), 3.41˜3.38 (m, 1H), 3.30˜3.24 (m, 2H), 3.14˜3.12 (m, 1H), 2.71˜2.67 (m, 1H), 2.58˜2.53 (m, 1H).

Workup

  1. customThe resulting reaction mixture
  2. customThe reaction was quenched with water (100 mL) when it
  3. extractionThe aqueous solution was extracted with EtOAc (80 mL×3)
  4. washThe combined organic phase was washed with brine
  5. concentrationconcentrated
  6. customto afford the crude product
  7. customThe residue was purified by silica gel column (eluted with PE/EA=5:1 to 1:2)

Sources & evidence

ORD record
ord-0eb64468af20477ca88198566260bdf5
Source dataset
uspto-grants-2016_09
Patent number
US09434733B2

Reaction notes

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