Dimethylformamide → HCID 59129228, compound

HRID 1908559Notes

Reaction equation

HRID 1908559 reaction equation
[C:1]([C:5]1[N:6]([C:31]2[C:32](C[C@H](O)C)=[C:33](S([O-])(=O)=O)C=CC=2C)[C:7]2[C:12]([CH:13]=1)=[CH:11][C:10]([NH:14][C:15]([C:17]1([C:20]3[CH:30]=[CH:29][C:23]4[O:24][C:25]([F:28])([F:27])[O:26][C:22]=4[CH:21]=3)[CH2:19][CH2:18]1)=[O:16])=[CH:9][CH:8]=2)([CH3:4])([CH3:3])[CH3:2].[N-:46]=[N+:47]=[N-:48].[Na+].CN(C=[O:54])C>>[N:46]([CH2:33][C@H:32]([OH:54])[CH2:31][N:6]1[C:7]2[C:12](=[CH:11][C:10]([NH:14][C:15]([C:17]3([C:20]4[CH:30]=[CH:29][C:23]5[O:24][C:25]([F:27])([F:28])[O:26][C:22]=5[CH:21]=4)[CH2:18][CH2:19]3)=[O:16])=[CH:9][CH:8]=2)[CH:13]=[C:5]1[C:1]([CH3:2])([CH3:4])[CH3:3])=[N+:47]=[N-:48]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 33557Sodium AzideHCID 86615739HCID 86615739, compound

Product 1

HCID 59129228HCID 59129228, compound

Conditions

Temperature
80 °C

Procedure

To a stirred solution (R)-3-(2-tert-butyl-5-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-1H-indol-1-yl)-2-hydroxypropyl-4-methylbenzenesulfonate (3.2 g, 5.0 mmol) in DMF (6 mL) was added sodium azide (2.0 g, 30 mmol). The reaction was heated at 80° C. for 2 h. The mixture was partitioned between 20 mL ethyl acetate and 20 mL water. The layers were separated and the organic layer was evaporated. The residue was purified using column chromatography (0-85% ethyl acetate/hexane) to give (R)—N-(1-(3-azido-2-hydroxypropyl)-2-tert-butyl-1H-indol-5-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-cyclopropanecarboxamide (2.48 g). LC/MS (M+1)=512.5. 1H NMR (400 MHz, CDCl3) δ 7.55 (d, 1H, J=2 Hz), 7.31 (m, 3H), 6.96 (s, 1H), 6.94 (dd, 1H, J=2, 8 Hz), 6.22 (s, 1H), 4.33 (m, 1H), 4.31 (dd, 1H, J=6, 15 Hz), 4.28 (dd, 1H, J=11, 15 Hz), 4.18 (m, 1H), 3.40 (dd, 1H, J=3, 6 Hz), 3.36 (dd, 1H, J=3, 6 Hz), 2.40 (br s, 1H), 1.74 (m, 2H), 1.40 (s, 9H), 1.11 (m, 2H).

Workup

  1. customThe mixture was partitioned between 20 mL ethyl acetate and 20 mL water
  2. customThe layers were separated
  3. customthe organic layer was evaporated
  4. customThe residue was purified

Sources & evidence

ORD record
ord-217159dbb9604f4a94122cecb63edcda
Source dataset
uspto-grants-2013_12
Patent number
US08598181B2

Reaction notes

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