1-Hydroxy-2-naphthoic acid → [5-tert-Butoxycarbonylamino-1-(6-chloro-5-(4-[(1-hydroxy-naphthalene-2-carbonyl)-amino]-phenylcarbamoyl)-pyridazin-3-yl)-piperidin-3-yl]-carbamic acid tert-butyl ester

HRID 1354832Notes

Reaction equation

HRID 1354832 reaction equation
CC[N:3]([CH:7]([CH3:9])[CH3:8])C(C)C.[C:10]([O:14][C:15]([NH:17][CH:18]1[CH2:23][CH:22]([NH:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][N:20]([C:32]2[N:37]=[N:36][C:35]([Cl:38])=[C:34]([C:39]([OH:41])=O)[CH:33]=2)[CH2:19]1)=[O:16])([CH3:13])([CH3:12])[CH3:11].[OH:42][C:43]1[C:52]2[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=2)[CH:46]=[CH:45][C:44]=1[C:53]([OH:55])=O.C1C=C[C:59]2N(O)N=[N:62][C:60]=2[CH:61]=1.CCN=C=NCCCN(C)C>C1COCC1.C(Cl)Cl>[C:28]([O:27][C:25](=[O:26])[NH:24][CH:22]1[CH2:23][CH:18]([NH:17][C:15]([O:14][C:10]([CH3:11])([CH3:12])[CH3:13])=[O:16])[CH2:19][N:20]([C:32]2[N:37]=[N:36][C:35]([Cl:38])=[C:34]([C:39](=[O:41])[NH:62][C:60]3[CH:61]=[CH:8][C:7]([NH:3][C:53]([C:44]4[CH:45]=[CH:46][C:47]5[C:52](=[CH:51][CH:50]=[CH:49][CH:48]=5)[C:43]=4[OH:42])=[O:55])=[CH:9][CH:59]=3)[CH:33]=2)[CH2:21]1)([CH3:31])([CH3:30])[CH3:29]

Participants

8

Reactant 5

HCID 68441-Hydroxy-2-naphthoic acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 588655196-(3,5-Bis-tert-butoxycarbonylamino-piperidin-1-yl)-3-chloro-pyridazine-4-carboxylic acid

Product 1

HCID 72447694[5-tert-Butoxycarbonylamino-1-(6-chloro-5-(4-[(1-hydroxy-naphthalene-2-carbonyl)-amino]-phenylcarbamoyl)-pyridazin-3-yl)-piperidin-3-yl]-carbamic acid tert-butyl esterYield 97,741.297%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

iPr2NEt (360 μL, 2 mmol) in THF (1 ml) was added to a mixture of 207 (483 mg, 1.02 mmol) and 1-hydroxy-naphthalene-2-carboxylic acid 111 (4-amino-phenyl)-amide (283.88 mg, 1.02 μmol) in THF (5 mL). HOBT (306.3 mg, 2 mmol) in THF (2 mL) was added. The reaction mixture was vortexed for 1 minute. EDCI (383.4 mg, 2 mmol) in CH2Cl2 (4 mL) was added into the above reaction mixture. The reaction mixture was shaken at room temperature for 16 h. The solvent was removed under reduced pressure. The solid was dissolved in CHCl3 (5 mL), washed with 10% NaHCO3 (3 mL), H2O (3 mL) and dried over MgSO4. Solvent was removed under reduced pressure. After flash chromatography purification using ethyl acetate and hexane, 730 mg of compound 209 (98.4% yield) was obtained as a solid. LC-MS (ESI): m/z=732.5 [M+1]+.

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionThe solid was dissolved in CHCl3 (5 mL)
  3. washwashed with 10% NaHCO3 (3 mL), H2O (3 mL)
  4. dry with materialdried over MgSO4
  5. customSolvent was removed under reduced pressure
  6. customAfter flash chromatography purification

Sources & evidence

ORD record
ord-3435241a7f8a49efae6732965fa7737e
Source dataset
uspto-grants-2007_05
Patent number
US07223759B2

Reaction notes

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