Formaldehyde → HCID 71667541, compound

HRID 1503924Notes

Reaction equation

HRID 1503924 reaction equation
Cl.[CH3:2][NH:3][C:4](=[O:31])[CH2:5][NH:6][C:7](=[O:30])[CH2:8][C@H:9]1[CH2:20][CH2:19][C:18]2[S:17][C:16]3[N:15]=[CH:14][N:13]=[C:12]([O:21][CH:22]4[CH2:27][CH2:26][CH:25]([NH:28][CH3:29])[CH2:24][CH2:23]4)[C:11]=3[C:10]1=2.C=O.[C:34]([BH3-])#N.[Na+]>CO>[CH3:29][N:28]([CH3:34])[CH:25]1[CH2:24][CH2:23][CH:22]([O:21][C:12]2[C:11]3[C:10]4[C@@H:9]([CH2:8][C:7]([NH:6][CH2:5][C:4]([NH:3][CH3:2])=[O:31])=[O:30])[CH2:20][CH2:19][C:18]=4[S:17][C:16]=3[N:15]=[CH:14][N:13]=2)[CH2:27][CH2:26]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 86695100HCID 86695100, compound

Product 1

HCID 71667541HCID 71667541, compoundYield 40.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of N-methyl-2-[2-[(3R)-12-[[4-(methylamino)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2 (6),9,11-tetraen-3-yl]acetamido]acetamide hydrochloride (105 mg, 0.22 mmol, 1.00 equiv) in 5 mL of methanol was added formaldehyde (37%, 1.0 mL) at room temperature under nitrogen for 1 h. Then sodium cyanoborohydride (59 mg, 0.97 mmol, 4.32 equiv) was added and stirred overnight at ambient temperature. The solvent was removed under reduced pressure and the crude product (100 mg, crude) was purified by preparative HPLC under the following conditions (SHIMADZU): column: SunFire Prep C18, 19*150 mm 5 um; mobile phase: water with 0.05% NH4CO3 and CH3CN (6.0% CH3CN up to 50.0% in 25 min); UV detection at 254/220 nm. The product containing fractions were collected and evaporated to remove the water and CH3CN to give 2-[2-[(3R)-12-[[4-(dimethylamino)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]acetamido]-N-methylacetamide (40 mg) as a white solid. MS: m/z 446 [M+H]+. 1H NMR (300 MHz, CD3OD) δ 8.37 (s, 1H), 5.20-5.12 (m, 1H), 3.74-3.68 (m, 3H), 3.20-2.84 (m, 3H), 2.65-2.47 (m, 4H), 2.36-2.17 (m, 11H), 1.95 (d, 2H), 1.59-1.51 (m, 4H).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe crude product (100 mg, crude) was purified by preparative HPLC under the following conditions (SHIMADZU)
  3. waitmobile phase: water with 0.05% NH4CO3 and CH3CN (6.0% CH3CN up to 50.0% in 25 min)
  4. additionThe product containing fractions
  5. customwere collected
  6. customevaporated
  7. customto remove the water and CH3CN

Sources & evidence

ORD record
ord-43f4c2b35f3e41f785f4688600ce4316
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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