Potassium Iodide → 2-{[(4-tert-Butoxycarbonylamino-butyl)-(3,4-dihydro-2H-pyrano[3,2-b]pyridin-4-yl)-amino]-methyl}-benzimidazole-1-carboxylic acid tert-butyl ester

HRID 899671Notes

Reaction equation

HRID 899671 reaction equation
[C:1]([O:5][C:6](=[O:23])[NH:7][CH2:8][CH2:9][CH2:10][CH2:11][NH:12][CH:13]1[C:18]2=[N:19][CH:20]=[CH:21][CH:22]=[C:17]2[O:16][CH2:15][CH2:14]1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)C(C)C)(C)C.[C:33]([O:37][C:38]([N:40]1[C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][C:43]=2[N:42]=[C:41]1[CH2:49]Cl)=[O:39])([CH3:36])([CH3:35])[CH3:34].[I-].[K+]>CC#N>[C:33]([O:37][C:38]([N:40]1[C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][C:43]=2[N:42]=[C:41]1[CH2:49][N:12]([CH2:11][CH2:10][CH2:9][CH2:8][NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:23])[CH:13]1[C:18]2=[N:19][CH:20]=[CH:21][CH:22]=[C:17]2[O:16][CH2:15][CH2:14]1)=[O:39])([CH3:36])([CH3:35])[CH3:34]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 81531DiisopropylethylamineHCID 15829159tert-Butyl 2-(chloromethyl)-1H-benzimidazole-1-carboxylateHCID 69296245[4-(3,4-Dihydro-2H-pyrano[3,2-b]pyridin-4-ylamino)-butyl]-carbamic acid tert-butyl ester

Product 1

HCID 691565352-{[(4-tert-Butoxycarbonylamino-butyl)-(3,4-dihydro-2H-pyrano[3,2-b]pyridin-4-yl)-amino]-methyl}-benzimidazole-1-carboxylic acid tert-butyl esterYield 67.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of [4-(3,4-Dihydro-2H-pyrano[3,2-b]pyridin-4-ylamino)-butyl]-carbamic acid tert-butyl ester (329 mg, 1.02 mmol) in CH3CN (5 mL) was added N,N-diisopropylethylamine (0.28 mL, 1.63 mmol) followed by 2-chloromethyl-benzimidazole-1-carboxylic acid tert-butyl ester (328 mg, 1.23 mmol) and potassium iodide (20 mg, 0.1 mmol). The resultant mixture was heated to 60° C. for 16 hours then cooled to room temperature. The mixture was concentrated and the residue was partitioned between CH2Cl2 (25 mL) and saturated aqueous NaHCO3 (20 mL). The phases were separated and the aqueous phase was extracted with CH2Cl2 (2×15 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated. Purification of the crude material by flash column chromatography on silica gel (CH2Cl2/MeOH/NH4OH, 95:4:1) provided 2-{[(4-tert-Butoxycarbonylamino-butyl)-(3,4-dihydro-2H-pyrano[3,2-b]pyridin-4-yl)-amino]-methyl}-benzimidazole-1-carboxylic acid tert-butyl ester (380 mg, 67%) as a white foam.

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was partitioned between CH2Cl2 (25 mL) and saturated aqueous NaHCO3 (20 mL)
  3. customThe phases were separated
  4. extractionthe aqueous phase was extracted with CH2Cl2 (2×15 mL)
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification of the crude material by flash column chromatography on silica gel (CH2Cl2/MeOH/NH4OH, 95:4:1)

Sources & evidence

ORD record
ord-eb5458fd479f4eacafcc48202422c1a6
Source dataset
uspto-grants-2008_04
Patent number
US07354932B2

Reaction notes

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