Dimethylformamide → HCID 118062072, compound

HRID 920782Notes

Reaction equation

HRID 920782 reaction equation
[F:1][C:2]1([F:11])[CH2:5][C:4]([CH2:9][F:10])(C(O)=O)[CH2:3]1.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.[Cl:29][C:30]1[CH:31]=[C:32]([C:36]2[C:44]([C:45]([NH2:47])=[O:46])=[C:39]3[CH2:40][NH:41][CH2:42][CH2:43][N:38]3[N:37]=2)[CH:33]=[CH:34][CH:35]=1.C[N:49]([CH:51]=[O:52])C>C1(C)C=CC=CC=1>[Cl:29][C:30]1[CH:31]=[C:32]([C:36]2[C:44]([C:45]([NH2:47])=[O:46])=[C:39]3[CH2:40][N:41]([C:51]([NH:49][C:4]4([CH2:9][F:10])[CH2:3][C:2]([F:1])([F:11])[CH2:5]4)=[O:52])[CH2:42][CH2:43][N:38]3[N:37]=2)[CH:33]=[CH:34][CH:35]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 199401P,P-Diphenylphosphinic azideHCID 118061124HCID 118061124, compoundHCID 1180626221773508-48-7

Product 1

HCID 118062072HCID 118062072, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
85 °C

Procedure

To a stirred solution of Intermediate 302E (26.7 mg, 0.159 mmol) in toluene (3 mL) was added TEA (0.101 mL, 0.723 mmol), DPPA (0.066 mL, 0.289 mmol) and the solution was heated to 85° C. for 1 hr. The reaction mass was cooled to RT and to it was added a solution of Intermediate 156E (40 mg, 0.145 mmol) in DMF (1 mL) and the reaction mixture was stirred at RT for 8 h. It was then concentrated and extracted with ethyl acetate (3×10 mL) The combined organic layer was dried over Na2SO4, filtered and the filtrate concentrated. The crude product was further purified by preparative HPLC to afford Compound 302 as an off-white solid (32 mg, 50%). HPLC retention times 1.41 min. and 1.41 min. (Methods E and L respectively). MS(ES): m/z=441 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.71 (t, J=1.76 Hz, 1H), 7.64 (dt, J=6.65, 1.95 Hz, 1H), 7.41-7.47 (m, 2H), 7.37 (s, 2H), 7.19 (br. s., 1H), 4.75 (s, 2H), 4.44-4.61 (m, 2H), 4.15 (t, J=5.52 Hz, 2H), 3.86 (t, J=5.52 Hz, 2H), 2.81 (t, J=12.30 Hz, 4H).

Workup

  1. temperatureThe reaction mass was cooled to RT and to it
  2. concentrationIt was then concentrated
  3. extractionextracted with ethyl acetate (3×10 mL) The combined organic layer
  4. dry with materialwas dried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated
  7. customThe crude product was further purified by preparative HPLC

Sources & evidence

ORD record
ord-80c1c40dead94c848ec26d1261c199b4
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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