HOAt → HCID 67080920, compound

HRID 1021419Notes

Reaction equation

HRID 1021419 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][C:14]1[CH:22]=[CH:21][C:17]([C:18]([OH:20])=O)=[CH:16][CH:15]=1)[O:9][CH2:8][CH2:7][CH:6]2[C:23]([O:25][CH3:26])=[O:24])#[N:2].C1C=NC2N(O)N=NC=2C=1.Cl.C(N=C=NCCCN(C)C)C.[NH2:49][C:50]1[CH:59]=[C:58]2[C:53]([CH2:54][CH2:55][N:56]([C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])[CH2:57]2)=[CH:52][CH:51]=1>CN(C)C=O.O>[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][C:14]1[CH:15]=[CH:16][C:17]([C:18]([NH:49][C:50]3[CH:59]=[C:58]4[C:53]([CH2:54][CH2:55][N:56]([C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])[CH2:57]4)=[CH:52][CH:51]=3)=[O:20])=[CH:21][CH:22]=1)[O:9][CH2:8][CH2:7][CH:6]2[C:23]([O:25][CH3:26])=[O:24])#[N:2]

Participants

7

Reactant 4

HCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22061016tert-Butyl 7-amino-3,4-dihydroisoquinoline-2(1H)-carboxylateHCID 462211084-(6-Cyano-4-(methoxycarbonyl)-chroman-7-yloxy)benzoic acid

Product 1

HCID 67080920HCID 67080920, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent3×

Procedure

To a stirred solution of 4-(6-cyano-4-(methoxycarbonyl)chroman-7-yloxy)benzoic acid (86 mg, 0.24 mmol) in N,N-dimethylformamide (0.5 mL) at ambient temperature was added a 0.6M solution of 7-aza-1-hydroxybenzotriazole in N,N-dimethylformamide (0.5 mL, 0.30 mmol), followed by solid 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (51 mg, 0.27 mmol). The resulting solution was stirred at ambient temperature for 1 hour. A solution of tert-butyl 7-amino-3,4-dihydroisoquinoline-2(1H)-carboxylate (66 mg, 0.27 mmol) in N,N-dimethylformamide (0.5 mL) was added. The resulting solution was stirred in an oil bath set to 50° C. for 21 hours. The solution was cooled to ambient temperature and diluted with water (15 mL). After stirring for a few minutes, the resulting precipitate was collected by filtration, washed with water, and dried under vacuum. This crude solid was purified by chromatography on silica gel, eluting with 50/50 hexanes/ethyl acetate, to afford tert-butyl 7-(4-(6-cyano-4-(methoxycarbonyl)chroman-7-yloxy)benzamido)-3,4-dihydroisoquinoline-2(1H)-carboxylate as an orange oil (84 mg, 59% yield).

Workup

  1. stirringThe resulting solution was stirred in an oil bath
  2. waitset to 50° C. for 21 hours
  3. temperatureThe solution was cooled to ambient temperature
  4. stirringAfter stirring for a few minutes
  5. filtrationthe resulting precipitate was collected by filtration
  6. washwashed with water
  7. customdried under vacuum
  8. customThis crude solid was purified by chromatography on silica gel
  9. washeluting with 50/50 hexanes/ethyl acetate

Sources & evidence

ORD record
ord-08b266192b244299b70b87ee383b09cb
Source dataset
uspto-grants-2014_05
Patent number
US08716498B2

Reaction notes

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