Formaldehyde → HCID 46865780, compound

HRID 1097545Notes

Reaction equation

HRID 1097545 reaction equation
[C:1]([BH3-])#N.[Na+].C1COCC1.[CH:10]1([C:16]2[C:17]3[CH:18]=[CH:19][C:20]([C:49]([NH:51][S:52]([CH:55]4[CH2:57][CH2:56]4)(=[O:54])=[O:53])=[O:50])=[CH:21][C:22]=3[N:23]3[CH2:29][C:28]([C:30]([N:32]4[CH2:39][C:38]56[CH2:40][NH:41][CH2:42][C:34]5([CH2:35][O:36][CH2:37]6)[CH2:33]4)=[O:31])=[CH:27][C:26]4[CH:43]=[C:44]([O:47][CH3:48])[CH:45]=[CH:46][C:25]=4[C:24]=23)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1.C=O>CO>[CH:10]1([C:16]2[C:17]3[CH:18]=[CH:19][C:20]([C:49]([NH:51][S:52]([CH:55]4[CH2:57][CH2:56]4)(=[O:53])=[O:54])=[O:50])=[CH:21][C:22]=3[N:23]3[CH2:29][C:28]([C:30]([N:32]4[CH2:39][C:38]56[CH2:40][N:41]([CH3:1])[CH2:42][C:34]5([CH2:35][O:36][CH2:37]6)[CH2:33]4)=[O:31])=[CH:27][C:26]4[CH:43]=[C:44]([O:47][CH3:48])[CH:45]=[CH:46][C:25]=4[C:24]=23)[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15]1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 8028TetrahydrofuranHCID 5003444Sodium cyanoborohydrideHCID 46896311HCID 46896311, compound

Product 1

HCID 46865780HCID 46865780, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A 1M solution of sodium cyanoborohydride in THF (0.15 mL, 0.15 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)-7H-indolo[2,1-a][2]benzazepine-10-carboxamide (Example 22) (10 mg, 0.015 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)-7H-indolo[2,1-a][2]benzazepine-10-carboxamide (7.9 mg, 9.4 μmol, 63% yield) as a bright yellow solid. LCMS: m/e 685 (M+H)+. LCMS retention time: 1.92 min. (Column: SunFire C18 5u 4.6×50 mm. Solvent A=90% Water/10% Acetonitrile/0.1% TFA. Solvent B=10% Water/90% Acetonitrile/0.1% TFA. Start % B=0. Final % B=100. Gradient Time=3 min. Flow Rate=4 mL/min.) 1H NMR (400 MHz, MeOD) δ ppm 8.09 (br s, 1H), 7.87 (d, J=8.5 Hz, 1H), 7.54 (br d, J=8.5 Hz, 1H), 7.53 (d, J=8.5 Hz, 1H), 7.14 (dd, J=8.5, 2.5 Hz, 1H), 7.10 (d, J=2.5 Hz, 1H), 7.07 (s, 1H), 5.22 (br d, J=14.8 Hz, 1H), 4.13-3.12 (m, 10H), 4.23 (br d, J=14.8 Hz, 1H), 3.90 (s, 3H), 2.97-2.76 (m, 5H), 2.15-1.67 (m, 6H), 1.52-1.07 (m, 8H).

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-0f1566954c2d4bc1996d31575cf24164
Source dataset
uspto-grants-2012_03
Patent number
US08143244B2

Reaction notes

Loading…