Formic Acid → 4-formamido-N-(1,1-dimethylethyl)-3-oxoandrosta-4,6-diene-17beta-carboxamide

HRID 654354Notes

Reaction equation

HRID 654354 reaction equation
[CH:1](O)=[O:2].C(OC(=O)C)(=O)C.[NH2:11][C:12]1[C:29](=[O:30])[CH2:28][CH2:27][C@@:26]2([CH3:31])[C:13]=1[CH:14]=[CH:15][C@@H:16]1[C@@H:25]2[CH2:24][CH2:23][C@@:21]2([CH3:22])[C@H:17]1[CH2:18][CH2:19][C@@H:20]2[C:32]([NH:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33]>O1CCCC1.O>[CH:1]([NH:11][C:12]1[C:29](=[O:30])[CH2:28][CH2:27][C@@:26]2([CH3:31])[C:13]=1[CH:14]=[CH:15][C@@H:16]1[C@@H:25]2[CH2:24][CH2:23][C@@:21]2([CH3:22])[C@H:17]1[CH2:18][CH2:19][C@@H:20]2[C:32]([NH:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])=[O:2]

Participants

6

Reactant 3

HCID 284Formic AcidHCID 7918Acetic AnhydrideHCID 677532974-amino-N-(1,1-dimethylethyl)-3-oxoandrosta-4,6-diene-17beta-carboxamide

Product 1

HCID 867459954-formamido-N-(1,1-dimethylethyl)-3-oxoandrosta-4,6-diene-17beta-carboxamideYield 67.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of formic acid (0.22 mL, 5.84 mmole) and acetic anhydride (0.46 mL, 4.76 mmole) was heated at reflux temperature for 2 hours under a nitrogen atmosphere. The cooled solution was diluted with tetrahydrofuran (5 mL) and a solution of 4-amino-N-(1,1-dimethylethyl)-3-oxoandrosta-4,6-diene-17β-carboxamide, (0.35 g, 0.91 mmole) in tetrahydrofuran (10 mL) was added. The reaction was stirred overnight at room temperature and then diluted with water (25 mL). A gummy material separated which was extracted into diethyl ether-dichloromethane and washed with saturated aqueous sodium bicarbonate. The dried solution was concentrated to a yellow foam which was purified by flash chromatography (hexane-50% ethyl acetate, ethyl acetate) to give 4-formamido-N-(1,1-dimethylethyl)-3-oxoandrosta-4,6-diene-17β-carboxamide (0.25 g, 67.6%, diethyl ether). IR 3440, 3304, 3246, 1684, 1670, 1650 cm-1 ; MS (CI) m/z 413 (100%, M+ +1); (EI) m/z 412 (18%, M+), 57 (100%); 1H NMR (CDCl3) δ 0.78 (3H, s, C18 -Me), 1.14 (3H, s, C19 -Me), 1.37 (s, 3× tBu-Me's), 5.11 (1H, s, NHCOBu), 6.15-6.45 (2H, m, C6 -H+C7 -H), 7.07-7.20 (1H, d+s, NHCO), 8.12+8.29 (1H, d+s, CHO).

Workup

  1. temperatureat reflux temperature for 2 hours under a nitrogen atmosphere
  2. customA gummy material separated which
  3. extractionwas extracted into diethyl ether-dichloromethane
  4. washwashed with saturated aqueous sodium bicarbonate
  5. concentrationThe dried solution was concentrated to a yellow foam which
  6. customwas purified by flash chromatography (hexane-50% ethyl acetate, ethyl acetate)

Sources & evidence

ORD record
ord-821cea7e9f044f3c8f3d563232ed1e02
Source dataset
uspto-grants-1992_07
Patent number
US05130424

Reaction notes

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