Formaldehyde → HCID 131719553, compound

HRID 743694Notes

Reaction equation

HRID 743694 reaction equation
[CH2:1]1[CH2:6][CH:5]([C:7]2([NH:22][C:23]([NH:25][C:26]3[CH:31]=[CH:30][C:29]([N:32]4[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]4)=[CH:28][CH:27]=3)=[O:24])[N:13]=[CH:12][C:11]3[CH:14]=[CH:15][CH:16]=[CH:17][C:10]=3[N:9]([CH2:18][CH2:19][CH3:20])[C:8]2=[O:21])[CH2:4][CH2:3][CH2:2]1.[C:38]([BH3-])#N.[Na+].C=O>CO.CC(OCC1C2C(=CC=CC=2)C(COC(C)=O)=C2C=1C=CC=C2)=O.O>[CH2:3]1[CH2:4][CH:5]([C:7]2([NH:22][C:23]([NH:25][C:26]3[CH:27]=[CH:28][C:29]([N:32]4[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]4)=[CH:30][CH:31]=3)=[O:24])[N:13]=[CH:12][C:11]3[CH:14]=[CH:15][CH:16]=[CH:17][C:10]=3[N:9]([CH2:18][CH2:19][CH3:20])[C:8]2=[O:21])[CH2:6][CH2:1][CH2:2]1

Participants

7

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 57057944HCID 57057944, compound

Product 1

HCID 131719553HCID 131719553, compoundYield 60.8%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 962WaterSolventHCID 613145Acetic acid 10-acetoxymethyl-anthracen-9-ylmethyl esterSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled (0° C.) and stirred solution of N-[3(R,S)-5-cyclohexyl-2,3-dihydro-2-oxo-1-propyl-1H-1,4-benzodiazepin-3-yl]N'-[4-(N-piperazinyl)phenyl]urea (96 mg) in methanol (4 ml) and glacial acetic add (49 μl) was added sodium cyanoborohydride (24 mg) followed by dropwise addition of a solution of formaldehyde (37 μl of a 38% (w/v) solution in water) in methanol (2 ml). The solution was stirred at 0° C. for 20 min then at room temperature for 1 h. After this time the solvent was removed in vacuo and the residue partitioned between dichloromethane (20 ml) and saturated potassium carbonate solution (20 ml). The organic phase was separated and the aqueous layer washed with dichloromethane (2×20 ml). The combined organic layers were washed with brine (20 ml), dried (Na2SO4) and evaporated in vacuo to afford a white solid. This was then chromatographed on silica gel, eluting with 90:10:1:1 dichloromethane:methanol:acetic acid:water to afford the title compound (60 mg) as a white solid. 1H NMR (360 MHz, D6 -DMSO) δ 0.73 (3H, t, J=7.4 Hz), 0.89-0.95 (1H, m), 1.10-1.70 (11H, m), 2.20 (3H, s), 2.40-2.43 (4H, m), 2.94-3.01 (5H, m), 3.60-3.70 (1H, m), 4.15-4.22 (1H, m), 5.02 (1H, d, J=8.9 Hz), 6.81 (2H, d, J=9 Hz), 7.12 (1H, d, J=8.6 Hz), 7.17 (2H, d, J=9 Hz), 7.35-7.39 (1H, m), 7.61-7.63 (2H, m), 7.76 (1H, d, J=7.8), 8.74 (1H, s). MS (CI, NH3) 517 (M+1).

Workup

  1. additionadd (49 μl)
  2. waitat room temperature for 1 h
  3. customAfter this time the solvent was removed in vacuo
  4. customthe residue partitioned between dichloromethane (20 ml) and saturated potassium carbonate solution (20 ml)
  5. customThe organic phase was separated
  6. washthe aqueous layer washed with dichloromethane (2×20 ml)
  7. washThe combined organic layers were washed with brine (20 ml)
  8. dry with materialdried (Na2SO4)
  9. customevaporated in vacuo
  10. customto afford a white solid
  11. customThis was then chromatographed on silica gel
  12. washeluting with 90:10:1:1 dichloromethane

Sources & evidence

ORD record
ord-565fffa2bd3c47909989fd0b52d27a71
Source dataset
uspto-grants-1996_09
Patent number
US05556969

Reaction notes

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