Diisopropylethylamine → HCID 59451651, compound

HRID 1874955Notes

Reaction equation

HRID 1874955 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Br:25][C:26]1[C:34]2[C:29](=[CH:30][CH:31]=[C:32]([O:35][CH2:36][CH2:37][OH:38])[CH:33]=2)[NH:28][C:27]=1[C:39]([OH:41])=O.[NH2:42][CH2:43][C:44]1[C:45]([F:61])=[C:46]([O:51][C:52]2[CH:53]=[C:54]([CH:57]=[C:58]([Cl:60])[CH:59]=2)[C:55]#[N:56])[C:47]([Cl:50])=[CH:48][CH:49]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[Br:25][C:26]1[C:34]2[C:29](=[CH:30][CH:31]=[C:32]([O:35][CH2:36][CH2:37][OH:38])[CH:33]=2)[NH:28][C:27]=1[C:39]([NH:42][CH2:43][C:44]1[CH:49]=[CH:48][C:47]([Cl:50])=[C:46]([O:51][C:52]2[CH:53]=[C:54]([C:55]#[N:56])[CH:57]=[C:58]([Cl:60])[CH:59]=2)[C:45]=1[F:61])=[O:41]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 594513923-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrileHCID 68485384HCID 68485384, compound

Product 1

HCID 59451651HCID 59451651, compoundYield 51.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HATU (0.061 g, 0.161 mmol) was added to a DMF (2 mL) solution of 3-bromo-5-[(2-hydroxyethyl)oxy]-1H-indole-2-carboxylic acid (0.048 g, 0.161 mmol), 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.050 g, 0.161 mmol) and DIPEA (0.028 mL, 0.161 mmol). The solution was stirred overnight and partitioned between water and EtOAc. The organic was washed with a 15% aqueous solution of Na2CO3, dried over MgSO4 and filtered. Evaporation of the EtOAc and trituration in acetone afforded the title compound (0.049 g, 47%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.91 (s, 1H), 8.49 (t, 1H), 7.77-7.89 (m, 1H), 7.51-7.57 (m, 2H), 7.43-7.51 (m, 2H), 7.37 (d, 1H), 6.96 (ddd, 1H), 6.89 (s, 1H), 4.86 (t, 1H), 4.62 (d, 2H), 4.02 (t, 1H), 3.69-3.82 (m, 1H). LCMS: m/z=592.2 (M+1).

Workup

  1. custompartitioned between water and EtOAc
  2. washThe organic was washed with a 15% aqueous solution of Na2CO3
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customEvaporation of the EtOAc and trituration in acetone

Sources & evidence

ORD record
ord-13dc791f233b4e87a1f0b317b126cac6
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

Loading…