Sodium hydride → HCID 22405512, compound

HRID 441170Notes

Reaction equation

HRID 441170 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:13](=[O:24])[NH:14][C:15]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:16][CH:17]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[Si:27]([O:34][CH:35]([C:45]([F:48])([F:47])[F:46])[CH:36]([NH:40][C:41](=[O:44])[CH2:42]I)[CH:37]([CH3:39])[CH3:38])([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28]>CN(C)C=O.Cl>[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:13](=[O:24])[N:14]([CH2:42][C:41]([NH:40][CH:36]([CH:37]([CH3:39])[CH3:38])[CH:35]([O:34][Si:27]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28])[C:45]([F:46])([F:48])[F:47])=[O:44])[C:15]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:16][CH:17]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 10479059HCID 10479059, compoundHCID 21851438HCID 21851438, compound

Product 1

HCID 22405512HCID 22405512, compoundYield 28.3%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolvent

Procedure

3-Benzyloxycarbonylamino-6-phenylpyrid-2-one (1.7 g) was added to a suspension of NaH (0.14 g) in dry dimethylformamide (50 mL). After 15 min stirring, the turbid, orange solution was treated with N-(2-tert-butyldimethylsilyloxy-3,3,3-trifluoro-1-isopropylpropyl)-2-iodoacetamide (2.65 g) and the mixture was stirred overnight. The mixture was diluted with 10% hydrochloric acid (125 mL) and extracted with ethyl acetate (2 times 150 mL). The combined extracts were washed with 10% hydrochloric acid and water (twice), dried and evaporated to an orange-brown glass. Purification by flash chromatography (gradient elution, 1%-4% ethyl acetate in dichloromethane) and overnight drying under vacuum yielded the N-alkylated product 2-(3-benzyloxycarbonylamino-2-oxo-6-phenyl-1,2-dihydro-1-pyridyl)-N-(2-tert-butyldimethylsilyloxy-3,3,3-trifluoro-1-isopropylpropyl)acetamide (0.97 g, 28%); TLC: Rf =0.35, dichloromethane:ethyl acetate (97:3); 300 MHz NMR: 0.08 (s,3), 0.10 (s, 3), 0.81 (d,3, J=6.6), 0.86 (s,9), 0.93 (d,3, J=6.6), 1.67-1.78 (m,1), 3.81 (t,1, J=10), 4.22-4.40 (m,2), 4.64 (broad d,1, J=15), 5.19 (s,2), 6.22 (d,1, J=7.6), 7.33-7.48 (m,10), 7.63 (d,1, J=9.9), 7.92 (d,1, J=7.6), 8.53 (s,1). Also obtained was the O-alkylated product 2-(3-benzyloxycarbonylamino-6-phenylpyrid-2-yloxy)-N-(2-tert-butyldimethylsilyloxy-3,3,3-trifluoro-1-isopropylpropyl)acetamide (2.11 g, 62%); TLC: Rf =0.61, dichloromethane:ethyl acetate (97:3), 300 MHz NMR: 0.01 (s,3), 0.07 (s,3), 0.75 (s,9), 0.77 (d, 3, J=6.6), 0.89 (d,3, J=6.6), 1.67-1.81 (m,1), 3.84 (t,1, J=10), 4.26 (m,1), 4.81 (d,1, J=15), 5.14 (d,1, J=15), 5.20 (s,2), 7.35-7.48 (m,9), 7.62 (d,1, J=8), 7.99 (dd,2, J=1.6, J=8.4), 8.12 (d,1, J=8), 9.31 (s,1); MS: m/z=646(M+1). (A mixed fraction (0.25 g, 7%) was also obtained).

Workup

  1. stirringthe mixture was stirred overnight
  2. extractionextracted with ethyl acetate (2 times 150 mL)
  3. washThe combined extracts were washed with 10% hydrochloric acid and water (twice),
  4. customdried
  5. customevaporated to an orange-brown glass
  6. customPurification
  7. washby flash chromatography (gradient elution, 1%-4% ethyl acetate in dichloromethane) and overnight
  8. customdrying under vacuum

Sources & evidence

ORD record
ord-3068937bb82b4a60beac05292b9b2bf6
Source dataset
uspto-grants-1996_05
Patent number
US05521179

Reaction notes

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