Triethylamine → HCID 67044209, compound

HRID 1964481Notes

Reaction equation

HRID 1964481 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]([OH:16])=O)[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1.S(Cl)(Cl)=O.[NH2:22][C:23]1[CH:24]=[C:25]2[C:29](=[CH:30][C:31]=1[F:32])[N:28]([CH2:33][C@@H:34]1[CH2:38][O:37][C:36]([CH3:40])([CH3:39])[O:35]1)[C:27]([C:41]([CH3:45])([CH3:44])[CH2:42][OH:43])=[CH:26]2.C(N(CC)CC)C>CN(C=O)C.ClCCl>[F:17][C:2]1([F:1])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:22][C:23]4[CH:24]=[C:25]5[C:29](=[CH:30][C:31]=4[F:32])[N:28]([CH2:33][C@@H:34]4[CH2:38][O:37][C:36]([CH3:39])([CH3:40])[O:35]4)[C:27]([C:41]([CH3:45])([CH3:44])[CH2:42][OH:43])=[CH:26]5)=[O:16])[CH2:12][CH2:13]3)=[CH:10][C:4]=2[O:3]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 442061031-(2,2-Difluoro-1,3-benzodioxol-5-yl)cyclopropanecarboxylic acidHCID 58201809HCID 58201809, compound

Product 1

HCID 67044209HCID 67044209, compoundYield 100%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

DMF (3 drops) was added to a stirring mixture of 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxylic acid (1.87 g, 7.7 mmol) and thionyl chloride (1.30 mL, 17.9 mmol). After 1 hour a clear solution had formed. The solution was concentrated under vacuum and then toluene (3 mL) was added and the mixture was concentrated again. The toluene step was repeated once more and the residue was placed on high vacuum for 10 minutes. The acid chloride was then dissolved in dichloromethane (10 mL) and added to a mixture of (R)-2-(5-amino-1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-1H-indol-2-yl)-2-methylpropan-1-ol (1.8 g, 5.4 mmol) and triethylamine (2.24 mL, 16.1 mmol) in dichloromethane (45 mL). The reaction was stirred at room temperature for 1 hour. The reaction was washed with 1N HCl solution, saturated NaHCO3 solution and brine, dried over MgSO4 and concentrated to yield the product as a black foamy solid (3 g, 100%). ESI-MS m/z calc. 560.6, found 561.7 (M+1)+. Retention time 2.05 minutes. 1H NMR (400 MHz, DMSO-d6) δ 8.31 (s, 1H), 7.53 (s, 1H), 7.42-7.40 (m, 2H), 7.34-7.30 (m, 3H), 6.24 (s, 1H), 4.51-4.48 (m, 1H), 4.39-4.34 (m,2H), 4.08 (dd, J=6.0, 8.3 Hz, 1H), 3.69 (t, J=7.6 Hz, 1H), 3.58-3.51 (m, 2H), 1.48-1.45 (m, 2H), 1.39 (s, 3H), 1.34-1.33 (m, 6H), 1.18 (s, 3H) and 1.14-1.12 (m, 2H) ppm

Workup

  1. customAfter 1 hour a clear solution had formed
  2. concentrationThe solution was concentrated under vacuum
  3. additiontoluene (3 mL) was added
  4. concentrationthe mixture was concentrated again
  5. dissolutionThe acid chloride was then dissolved in dichloromethane (10 mL)
  6. washThe reaction was washed with 1N HCl solution, saturated NaHCO3 solution and brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-3504d2c9ed4a41caa2a74f6b2dfd59d2
Source dataset
uspto-grants-2013_04
Patent number
US08415387B2

Reaction notes

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