Hydrochloric Acid → N-(4''-Amino-4,4-difluoro-5''-methyl-3'H-dispiro[cyclohexane-1,2'-indene-1',2''-imidazol]-6'-yl)-5-chloropyridine-2-carboxamide

HRID 539346Notes

Reaction equation

HRID 539346 reaction equation
Cl.CN(C)CCCN=C=NCC.[Cl:13][C:14]1[CH:15]=[CH:16][C:17]([C:20]([OH:22])=O)=[N:18][CH:19]=1.[F:23][C:24]1([F:45])[CH2:44][CH2:43][C:27]2([C:35]3([N:39]=[C:38]([NH2:40])[C:37]([CH3:41])=[N:36]3)[C:34]3[C:29](=[CH:30][CH:31]=[C:32]([NH2:42])[CH:33]=3)[CH2:28]2)[CH2:26][CH2:25]1.Cl>C(Cl)Cl.CN(C=O)C>[NH2:40][C:38]1[C:37]([CH3:41])=[N:36][C:35]2([C:34]3[C:29](=[CH:30][CH:31]=[C:32]([NH:42][C:20]([C:17]4[CH:16]=[CH:15][C:14]([Cl:13])=[CH:19][N:18]=4)=[O:22])[CH:33]=3)[CH2:28][C:27]32[CH2:26][CH2:25][C:24]([F:45])([F:23])[CH2:44][CH2:43]3)[N:39]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27628725-Chloro-2-picolinic acidHCID 573861504,4-difluoro-5''-methyl-3'H-dispiro[cyclohexane-1,2'-indene-1',2''-imidazole]-4'',6'-diamine

Product 1

HCID 67979524N-(4''-Amino-4,4-difluoro-5''-methyl-3'H-dispiro[cyclohexane-1,2'-indene-1',2''-imidazol]-6'-yl)-5-chloropyridine-2-carboxamideYield 17.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (36 mg, 0.19 mmol) was added to a suspension of 5-chloropicolinic acid (27 mg, 0.17 mmol) in DCM (0.5 mL). The obtained orange solution was stirred for 5 min and then added dropwise over 2 min to an ice-cooled solution of 4,4-difluoro-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazole]-4″,6′-diamine (Example 28d Step 1, 46 mg, 0.14 mmol) and 2M aq. HCl (0.072 mL, 0.14 mmol) in DMF (0.5 mL). The mixture was stirred at 0° C. for 10 min and was then allowed to reach r.t. overnight. The solvent was evaporated. The crude was purified using preparative chromatography to give the title compound (11 mg, 17% yield): 1H NMR (500 MHz, DMSO-d6) δ ppm 1.23 (d, 1 H), 1.51 (d, 2 H), 1.66-1.98 (m, 5 H), 2.18 (s, 3 H), 2.99 (d, 1 H), 3.08 (d, 1 H), 6.63 (br. s., 1 H), 7.23-7.29 (m, 2 H), 7.62 (d, 1 H), 8.10 (d, 1 H), 8.18 (dd, 1 H), 8.74 (s, 1 H), 10.50 (s, 1 H); MS (APCI+) m/z 458.1 [M+H]+.

Workup

  1. stirringThe mixture was stirred at 0° C. for 10 min
  2. waitto reach r.t. overnight
  3. customThe solvent was evaporated
  4. customThe crude was purified

Sources & evidence

ORD record
ord-549185fe2432402ea450302b0c2cc75b
Source dataset
uspto-grants-2014_10
Patent number
US08865911B2

Reaction notes

Loading…