Triethylamine → N-(2-tert-butyl-4-cyano-1-(2-hydroxyethyl)-1H-indol-5-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide

HRID 2038122Notes

Reaction equation

HRID 2038122 reaction equation
[F:1][C:2]1([F:17])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14](Cl)=[O:15])[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1.[NH2:18][C:19]1[CH:27]=[CH:26][C:25]2[N:24]([CH2:28][CH2:29][OH:30])[C:23]([C:31]([CH3:34])([CH3:33])[CH3:32])=[CH:22][C:21]=2[C:20]=1[C:35]#[N:36].C(N(CC)CC)C>ClCCl>[C:31]([C:23]1[N:24]([CH2:28][CH2:29][OH:30])[C:25]2[C:21]([CH:22]=1)=[C:20]([C:35]#[N:36])[C:19]([NH:18][C:14]([C:11]1([C:9]3[CH:8]=[CH:7][C:5]4[O:6][C:2]([F:17])([F:1])[O:3][C:4]=4[CH:10]=3)[CH2:13][CH2:12]1)=[O:15])=[CH:27][CH:26]=2)([CH3:34])([CH3:32])[CH3:33]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 575168501-(2,2-Difluoro-1,3-benzodioxol-5-yl)cyclopropanecarbonyl chlorideHCID 581832225-amino-2-tert-butyl-1-(2-hydroxyethyl)-1H-indole-4-carbonitrile

Product 1

HCID 46199645N-(2-tert-butyl-4-cyano-1-(2-hydroxyethyl)-1H-indol-5-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarbonyl chloride (196 mg, 0.75 mmol) was added to a solution of 5-amino-2-tert-butyl-1-(2-hydroxyethyl)-1H-indole-4-carbonitrile (150 mg, 0.58 mmol) and triethylamine (242 μL, 1.74 mmol) in dichloromethane (2 mL). The reaction was stirred at room temperature overnight. The reaction mixture was diluted with dichloromethane and extracted with 1N HCl solution (×2), saturated NaHCO3 solution (×2), brine, dried over MgSO4, filtered and concentrated. The residue was dissolved in DMSO and purified by reverse-phase HPLC to yield the product, N-(2-tert-butyl-4-cyano-1-(2-hydroxyethyl)-1H-indol-5-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide. ESI-MS m/z calc. 481.2, found 482.5 (M+1)+. Retention time 1.99 minutes. 1H NMR (400 MHz, DMSO-d6) δ 8.93 (s, 1H), 7.71 (d, J=8.8 Hz, 1H), 7.51 (s, 1H), 7.42 (d, J=8.3 Hz, 1H), 7.33 (d, J=1.6 Hz, 1H), 7.08 (d, J=8.8 Hz, 1H), 6.28 (s, 5.05 (t, J=5.6 Hz, 1H), 4.42 (t, J=6.8 Hz, 2H), 3.70-3.65 (m, 2H), 1.51-1.48 (m, 2H), 1.44 (s, 9H), 1.19-1.16 (m, 2H).

Workup

  1. extractionextracted with 1N HCl solution (×2), saturated NaHCO3 solution (×2), brine
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in DMSO
  6. custompurified by reverse-phase HPLC

Sources & evidence

ORD record
ord-ada50115041f442f9cc8de330e05d48a
Source dataset
uspto-grants-2013_11
Patent number
US08575209B2

Reaction notes

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