Triethylamine → 5-[bis(Cyclopropylmethyl)amino]-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-indole-2-carboxamide

HRID 1874841Notes

Reaction equation

HRID 1874841 reaction equation
[CH2:1]([N:3]([CH2:6][CH3:7])[CH2:4][CH3:5])[CH3:2].F[C:9](F)(F)[C:10](O)=O.NC1[CH:17]=[C:18]2[C:22](=[CH:23]C=1)[NH:21][C:20]([C:25]([NH:27][CH2:28][C:29]1[CH:34]=[CH:33][C:32]([Cl:35])=[C:31]([O:36][C:37]3[CH:42]=[C:41]([C:43]#[N:44])[CH:40]=[C:39]([Cl:45])[CH:38]=3)[C:30]=1[F:46])=[O:26])=[CH:19]2.[CH:47]1(C=O)C[CH2:48]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C.C(OCC)(=O)C>[CH:2]1([CH2:1][N:3]([CH2:6][CH:7]2[CH2:10][CH2:9]2)[C:4]2[CH:17]=[C:18]3[C:22](=[CH:23][CH:5]=2)[NH:21][C:20]([C:25]([NH:27][CH2:28][C:29]2[CH:34]=[CH:33][C:32]([Cl:35])=[C:31]([O:36][C:37]4[CH:42]=[C:41]([C:43]#[N:44])[CH:40]=[C:39]([Cl:45])[CH:38]=4)[C:30]=2[F:46])=[O:26])=[CH:19]3)[CH2:48][CH2:47]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 123114CyclopropanecarboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 866448845-amino-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-indole-2-carboxamide trifluoroacetate

Product 1

HCID 684872255-[bis(Cyclopropylmethyl)amino]-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-indole-2-carboxamideYield 37%

Reagents, catalysts & solvents 2

HCID 63651,1-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Triethylamine (0.049 mL, 0.355 mmol) was added to a suspension of 5-amino-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-indole-2-carboxamide trifluoroacetate (0.207 g, 0.355 mmol) in dichloroethane (5 mL). To the resulting solution was added cyclopropanecarbaldehyde (0.027 mL, 0.355 mmol) and sodium triacetoxyborohydride (0.188 g, 0.887 mmol). After stirring at RT overnight, the reaction mixture was diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate. The organic layer was dried over sodium sulfate and concentrated. The residue was purified by column chromatography (dichloromethane/methanol) to give the title compound (0.075 g, 37%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 11.23 (d, 1H), 8.89 (t, 1H), 7.80 (d, 1H), 7.43-7.55 (m, 3H), 7.33-7.41 (m, 1H), 7.24 (d, 1H), 6.86-7.00 (m, 3H), 4.54 (d, 2H), 3.16 (d, 4H), 0.75-1.05 (m, 2H), 0.21-0.57 (m, 4H), −0.05-0.26 (m, 4H). MS: m/z 577 (M+1).

Workup

  1. washwashed with saturated aqueous sodium bicarbonate
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. concentrationconcentrated
  4. customThe residue was purified by column chromatography (dichloromethane/methanol)

Sources & evidence

ORD record
ord-41c73b94fd72403e97071740de14e22f
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

Loading…