Formaldehyde → HCID 46896525, compound

HRID 1097546Notes

Reaction equation

HRID 1097546 reaction equation
[C:1]([BH3-])#N.[Na+].[CH:5]1([C:11]2[C:12]3[CH:13]=[CH:14][C:15]([C:44]([NH:46][S:47]([CH:50]4[CH2:52][CH2:51]4)(=[O:49])=[O:48])=[O:45])=[CH:16][C:17]=3[N:18]3[CH2:24][CH:23]([C:25]([N:27]4[CH2:34][C:33]56[CH2:35][NH:36][CH2:37][C:29]5([CH2:30][O:31][CH2:32]6)[CH2:28]4)=[O:26])[CH2:22][C:21]4[CH:38]=[C:39]([O:42][CH3:43])[CH:40]=[CH:41][C:20]=4[C:19]=23)[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1.C=O>CO>[CH:5]1([C:11]2[C:12]3[CH:13]=[CH:14][C:15]([C:44]([NH:46][S:47]([CH:50]4[CH2:52][CH2:51]4)(=[O:48])=[O:49])=[O:45])=[CH:16][C:17]=3[N:18]3[CH2:24][CH:23]([C:25]([N:27]4[CH2:34][C:33]56[CH2:35][N:36]([CH3:1])[CH2:37][C:29]5([CH2:30][O:31][CH2:32]6)[CH2:28]4)=[O:26])[CH2:22][C:21]4[CH:38]=[C:39]([O:42][CH3:43])[CH:40]=[CH:41][C:20]=4[C:19]=23)[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 46896410HCID 46896410, compound

Product 1

HCID 46896525HCID 46896525, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A 1M solution of sodium cyanoborohydride in THE (0.16 mL, 0.16 mmol) was added to a solution of 13-cyclohexyl-N-(cyclopropylsulfonyl)-3-methoxy-6-(3-oxa-7,10-diazatricyclo[3.3.3.01,5]undec-7-ylcarbonyl)-6,7-dihydro-5H-indolo[2,1-a][2]benzazepine-10-carboxamide (Example 24A) (11 mg, 0.016 mmol) and formaldehyde (37 wt. % in water) (0.01 mL, 0.1 mmol) in MeOH (1 mL) and the mixture was stirred at rt for 16 h. The reaction was concentrated, dissolved into MeOH, filtered and purified by preparative HPLC (H2O-MeOH with 0.1% TFA buffer) to yield 13-cyclohexyl-N-(cyclopropylsulfonyl)-3-methoxy-6-((10-methyl-3-oxa-7,10-diazatricyclo[3.3.3.01,5]undec-7-yl)carbonyl)-6,7-dihydro-5H-indolo[2,1-a][2]benzazepine-10-carboxamide (12 mg, 0.013 mmol, 82% yield) as a yellow solid. LCMS: m/e 687 (M+H)+. LCMS retention time: 2.47 min. (Column: Phenomenex-Luna 3.0×50 mm S10. Solvent A=90% Water: 10% Methanol: 0.1% TFA. Solvent B=10% Water: 90% Methanol: 0.1% TFA. Start % B=0. Final % B=100. Gradient Time=3 min. Flow Rate=4 mL/min).

Workup

  1. concentrationThe reaction was concentrated
  2. dissolutiondissolved into MeOH
  3. filtrationfiltered
  4. custompurified by preparative HPLC (H2O-MeOH with 0.1% TFA buffer)

Sources & evidence

ORD record
ord-3eed611f20604a56a26b235b27b1fad8
Source dataset
uspto-grants-2012_03
Patent number
US08143244B2

Reaction notes

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