Formaldehyde → 1-N-(2-fluoroethyl)-1-N-methyl-4-N-[7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]cyclohexane-1,4-diamine

HRID 525114Notes

Reaction equation

HRID 525114 reaction equation
[F:1][CH2:2][CH2:3][NH:4][CH:5]1[CH2:10][CH2:9][CH:8]([NH:11][C:12]2[C:23]3[C:22]4[CH2:21][CH2:20][CH2:19][C:18]=4[S:17][C:16]=3[N:15]=[CH:14][N:13]=2)[CH2:7][CH2:6]1.C=O.[BH-](OC(C)=O)(OC(C)=O)O[C:28](C)=O.[Na+]>CO>[F:1][CH2:2][CH2:3][N:4]([CH3:28])[CH:5]1[CH2:10][CH2:9][CH:8]([NH:11][C:12]2[C:23]3[C:22]4[CH2:21][CH2:20][CH2:19][C:18]=4[S:17][C:16]=3[N:15]=[CH:14][N:13]=2)[CH2:7][CH2:6]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 866733361-N-(2-fluoroethyl)-4-N-[7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]cyclohexane-1,4-diamine

Product 1

HCID 575199931-N-(2-fluoroethyl)-1-N-methyl-4-N-[7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]cyclohexane-1,4-diamineYield 46%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 1-N-(2-fluoroethyl)-4-N-[7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]cyclohexane-1,4-diamine (100 mg, 0.30 mmol, 1.00 equiv) in methanol (10 mL) was added HCHO (37%, 1 mL) and the resulting mixture was stirred at room temperature for 0.5 h. The NaBH(OAc)3 (250 mg, 1.18 mmol, 4.00 equiv) was added and the resulting solution was stirred for additional 1 h at ambient temperature. After completion of the reaction, the reaction was then quenched with saturated aqueous sodium bicarbonate, extracted with 3×50 ml of dichloromethane. The combined organic layers were dried in an oven under reduced pressure and concentrated under vacuum. The residue was applied onto a silica gel column with dichloromethane/MeOH (10:1) to afford the corresponding 1-N-(2-fluoroethyl)-1-N-methyl-4-N-[7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]cyclohexane-1,4-diamine (47.8 mg, 46%) as a white solid. MS: (ES, m/z): 349 [M+H]+. 1H NMR (400 MHz, CDCl3): δ 1.23-1.32 (m, 2H), 1.50-1.60 (m, 2H), 1.76-1.95 (m, 2H), 2.27-2.35 (m, 2H), 2.40 (s, 3H), 2.50-2.60 (m, 3H), 2.84 (d, 2H), 2.99-3.05 (m, 4H), 4.05-4.15 (m, 1H), 4.57 (d, 2H), 4.86 (d, 1H), 8.39 (s, 1H).

Workup

  1. stirringthe resulting solution was stirred for additional 1 h at ambient temperature
  2. customAfter completion of the reaction
  3. customthe reaction was then quenched with saturated aqueous sodium bicarbonate
  4. extractionextracted with 3×50 ml of dichloromethane
  5. customThe combined organic layers were dried in an oven under reduced pressure
  6. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-6a75a4b61bf8440e8131396408b40e37
Source dataset
uspto-grants-2016_05
Patent number
US09340554B2

Reaction notes

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