Diisopropylethylamine → {4-[(3-Chloro-4-fluoro-benzo[b]thiophene-2-carbonyl)-(2-methoxy-5-pyridin-3-yl-benzyl)-amino]-cyclohexyl}-carbamic acid tert-butyl ester

HRID 2389713Notes

Reaction equation

HRID 2389713 reaction equation
[C:1]([O:5][C:6](=[O:30])[NH:7][CH:8]1[CH2:13][CH2:12][CH:11]([NH:14][CH2:15][C:16]2[CH:21]=[C:20]([C:22]3[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=3)[CH:19]=[CH:18][C:17]=2[O:28][CH3:29])[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)C(C)C)(C)C.[Cl:40][C:41]1[C:42]2[C:52]([F:53])=[CH:51][CH:50]=[CH:49][C:43]=2[S:44][C:45]=1[C:46](Cl)=[O:47]>C(Cl)Cl>[C:1]([O:5][C:6](=[O:30])[NH:7][CH:8]1[CH2:9][CH2:10][CH:11]([N:14]([C:46]([C:45]2[S:44][C:43]3[CH:49]=[CH:50][CH:51]=[C:52]([F:53])[C:42]=3[C:41]=2[Cl:40])=[O:47])[CH2:15][C:16]2[CH:21]=[C:20]([C:22]3[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=3)[CH:19]=[CH:18][C:17]=2[O:28][CH3:29])[CH2:12][CH2:13]1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 125946453-Chloro-4-fluoro-1-benzothiophene-2-carbonyl chlorideHCID 59766919[4-(2-Methoxy-5-pyridin-3-yl-benzylamino)-cyclohexyl]-carbamic acid tert-butyl ester

Product 1

HCID 59775680{4-[(3-Chloro-4-fluoro-benzo[b]thiophene-2-carbonyl)-(2-methoxy-5-pyridin-3-yl-benzyl)-amino]-cyclohexyl}-carbamic acid tert-butyl esterYield 59%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N3 is prepared according to a method similar to Method D. [4-(2-methoxy-5-pyridin-3-yl-benzylamino)-cyclohexyl]-carbamic acid tert-butyl ester (N2) (1.035 g, 2.52 mmol) is dissolved in 10 mL anhydrous methylene chloride. N,N-Diisopropylethylamine (0.526 mL, 3.02 mmol) is added followed by 3-chloro-4-fluoro-benzo[b]thiophene-2-carbonyl chloride (6) (0.690 g, 2.77 mmol). The mixture is allowed to stir overnight at room temperature and then is partitioned between ethyl acetate and water. The organic phase is dried (MgSO4) and evaporated, and the residue is chromatographed on silica gel using a gradient elution of methanol/methylene chloride. {4-[(3-Chloro-4-fluoro-benzo[b]thiophene-2-carbonyl)-(2-methoxy-5-pyridin-3-yl-benzyl)-amino]-cyclohexyl}-carbamic acid tert-butyl ester (N3) is obtained (0.93 g, 1.48 mmol; 59% yield).

Workup

  1. customN3 is prepared
  2. customis partitioned between ethyl acetate and water
  3. dry with materialThe organic phase is dried (MgSO4)
  4. customevaporated
  5. customthe residue is chromatographed on silica gel using
  6. washa gradient elution of methanol/methylene chloride

Sources & evidence

ORD record
ord-76ac9c7748bd4bb2bfca6b8e8c2ba517
Source dataset
uspto-grants-2012_09
Patent number
US08273747B2

Reaction notes

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