Water → tert-Butyl N-(cyclopropylmethyl)-N-[(4-oxo-4,5,7,8-tetrahydro-3H-pyrano[4,3-d]pyrimidin-2-yl)methyl]carbamate

HRID 713394Notes

Reaction equation

HRID 713394 reaction equation
[H-].[Na+].Cl[CH2:4][C:5]1[NH:6][C:7](=[O:15])[C:8]2[CH2:14][O:13][CH2:12][CH2:11][C:9]=2[N:10]=1.[CH:16]1([CH2:19][NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:18][CH2:17]1.O>CN(C=O)C>[CH:16]1([CH2:19][N:20]([CH2:4][C:5]2[NH:6][C:7](=[O:15])[C:8]3[CH2:14][O:13][CH2:12][CH2:11][C:9]=3[N:10]=2)[C:21](=[O:27])[O:22][C:23]([CH3:25])([CH3:24])[CH3:26])[CH2:17][CH2:18]1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 49757579tert-butyl N-(cyclopropylmethyl)carbamateHCID 1357419472-(Chloromethyl)-7,8-dihydro-3H-pyrano[4,3-D]pyrimidin-4(5H)-one

Product 1

HCID 136627243tert-Butyl N-(cyclopropylmethyl)-N-[(4-oxo-4,5,7,8-tetrahydro-3H-pyrano[4,3-d]pyrimidin-2-yl)methyl]carbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of NaH (11.96 g, 299 mmol) in 260 mL DMF at 0° C. was sequentially added 2-(chloromethyl)-7,8-dihydro-3H-pyrano[4,3-d]pyrimidin-4(5H)-one (20 g, 100 mmol) and tert-butyl cyclopropylmethylcarbamate (17.07 g, 100 mmol) in small portions in order to maintain the internal temperature at or below 5° C. The reaction mixture was allowed to warm to room temperature slowly with continued stirring over 12 h. The reaction was cooled to 0 C and water was added slowly (˜250 mL total). The reaction mixture was concentrated in vacuo, taken up in ethyl acetate, filtered and concentrated to a red oil. The material was purified on a pad of silica gel, loading with 20% ethyl acetate in heptanes and eluting with 100% ethyl acetate via a sharp gradient. The title compound was obtained as an off-white solid (20.79 g).

Workup

  1. customat 0° C.
  2. temperatureto maintain the internal temperature at or below 5° C
  3. additionwas added slowly (˜250 mL total)
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. filtrationfiltered
  6. concentrationconcentrated to a red oil
  7. customThe material was purified on a pad of silica gel, loading with 20% ethyl acetate in heptanes
  8. washeluting with 100% ethyl acetate via a sharp gradient

Sources & evidence

ORD record
ord-1c9be2b051b74977915b78e5e523d3be
Source dataset
uspto-grants-2015_11
Patent number
US09181266B2

Reaction notes

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