Formaldehyde → HCID 178483898, compound

HRID 1743803Notes

Reaction equation

HRID 1743803 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][C:5]([N:8]([CH3:23])[CH2:9][CH2:10][C@H:11]2[CH2:16][CH2:15][C@H:14]([CH2:17][NH:18][CH2:19][CH2:20][CH2:21][OH:22])[CH2:13][CH2:12]2)=[N:6][CH:7]=1.[CH2:24]=O.P(O)(O)O>O1CCOCC1>[Br:1][C:2]1[CH:7]=[N:6][C:5]([N:8]([CH3:23])[CH2:9][CH2:10][C@H:11]2[CH2:16][CH2:15][C@H:14]([CH2:17][N:18]([CH3:24])[CH2:19][CH2:20][CH2:21][OH:22])[CH2:13][CH2:12]2)=[N:4][CH:3]=1

Participants

5

Reactant 3

HCID 712Formaldehyde2×HCID 107909Phosphorous acidHCID 178483645HCID 178483645, compound

Product 1

HCID 178483898HCID 178483898, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 0.21 g (0.6 mmol) trans-3-[(4-{2-[(5-Bromo-pyrimidin-2-yl)-methyl-amino]-ethyl}-cyclohexylmethyl)-amino]-propan-1-ol was taken up in 3 ml of dioxan, treated with 3 ml of a aqueous 1N NaH2PO3 solution and 3 ml of a 36% aqueous formaldehyde solution (Loibner, H., A. Pruckner, et al. (1984). “Reductive methylation of primary and secondary amines with formaldehyde and phosphorous acid salts.” Tetrahedron Lett. 25(24): 2535–6). The mixture was heated to 60° C. for 30 min. The mixture was cooled and extracted with 2N NaOH/ether (3×). The organic phase was washed with aqueous 10% NaCl, dried (NaSO4) and evaporated. Purification by flash silica gel column (CH2Cl2/MeOH 98:2 to 9:1) gave 0.17 g (76%) of trans-3-[(4-{2-[(5-Bromo-pyrimidin-2-yl)-methyl-amino]-ethyl}-cyclohexylmethyl)-methyl-amino]-propan-1-ol, MS: 399 (MH+, 1Br).

Workup

  1. temperatureThe mixture was cooled
  2. extractionextracted with 2N NaOH/ether (3×)
  3. washThe organic phase was washed with aqueous 10% NaCl
  4. dry with materialdried (NaSO4)
  5. customevaporated
  6. customPurification by flash silica gel column (CH2Cl2/MeOH 98:2 to 9:1)

Sources & evidence

ORD record
ord-82e7e03340aa46c9a6a595014695cf2b
Source dataset
uspto-grants-2006_03
Patent number
US07012077B2

Reaction notes

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