Sodium triacetoxyborohydride → 9-(3-Hydroxy-8-methyl-8-aza-bicyclo[3.2.1]oct-3-ylethynyl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amide

HRID 575077Notes

Reaction equation

HRID 575077 reaction equation
[OH:1][C:2]1([C:10]#[C:11][C:12]2[CH:13]=[CH:14][C:15]3[O:21][CH2:20][CH2:19][N:18]4[CH:22]=[C:23]([C:25]([NH2:27])=[O:26])[N:24]=[C:17]4[C:16]=3[CH:28]=2)[CH2:8][C@H:7]2[NH:9][C@H:4]([CH2:5][CH2:6]2)[CH2:3]1.[BH-](OC(C)=O)(OC(C)=O)O[C:31](C)=O.[Na+]>CO>[OH:1][C:2]1([C:10]#[C:11][C:12]2[CH:13]=[CH:14][C:15]3[O:21][CH2:20][CH2:19][N:18]4[C:17](=[N:24][C:23]([C:25]([NH2:27])=[O:26])=[CH:22]4)[C:16]=3[CH:28]=2)[CH2:3][CH:4]2[N:9]([CH3:31])[CH:7]([CH2:6][CH2:5]2)[CH2:8]1

Participants

4

Reactant 2

HCID 5049666Sodium triacetoxyborohydrideHCID 8669310310-(((1R,5S)-3-hydroxy-8-azabicyclo[3.2.1]octan-3-yl)ethynyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide

Product 1

HCID 717147339-(3-Hydroxy-8-methyl-8-aza-bicyclo[3.2.1]oct-3-ylethynyl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amideYield 8.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

In a solution of 10-(((1R,5S)-3-hydroxy-8-azabicyclo[3.2.1]octan-3-yl)ethynyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide (0.15 g, 0.4 mmol) in methanol (20 ml) was added (HCHO)n (144 mg, 4.8 mmol) and NaBH(OAc)3 (260 mg, 1.2 mmol). The solution was stirred for 1 h at room temperature. The reaction mixture was quenched with water and purified by Prep HPLC to afford 9-(3-Hydroxy-8-methyl-8-aza-bicyclo[3.2.1]oct-3-ylethynyl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amide (13.5 mg, 8.5%). 1H NMR (Methanol-d4, 400 MHz): δ 8.30 (m, 1H), 8.10 (s, 1H), 7.56 (d, J=8.4 Hz, 1H), 7.19 (d, J=8.4 Hz, 1H), 4.67 (s, 4H), 3.94 (s, 2H), 2.81 (s, 3H), 2.65-2.20 (m, 8H). LCMS [M+H]+=393.0.

Workup

  1. customThe reaction mixture was quenched with water
  2. custompurified by Prep HPLC

Sources & evidence

ORD record
ord-7934add0e6e64180bf6159384d4230c4
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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