Benzaldehyde → 1-((3R)-6,8-Difluoro-3,4-dihydro-2H-1-benzopyran-3-yl)-1,3-dihydro-5-(2-((phenylmethyl)amino)ethyl)-2H-imidazole-2-thione

HRID 538943Notes

Reaction equation

HRID 538943 reaction equation
Cl.[NH2:2][CH2:3][CH2:4][C:5]1[N:9]([C@@H:10]2[CH2:19][C:18]3[C:13](=[C:14]([F:21])[CH:15]=[C:16]([F:20])[CH:17]=3)[O:12][CH2:11]2)[C:8](=[S:22])[NH:7][CH:6]=1.[CH:23](=O)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CC(O)C>[CH2:23]([NH:2][CH2:3][CH2:4][C:5]1[N:9]([C@@H:10]2[CH2:19][C:18]3[C:13](=[C:14]([F:21])[CH:15]=[C:16]([F:20])[CH:17]=3)[O:12][CH2:11]2)[C:8](=[S:22])[NH:7][CH:6]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

5

Reactant 3

HCID 240BenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 10450386Etamicastat HCl salt

Product 1

HCID 250526301-((3R)-6,8-Difluoro-3,4-dihydro-2H-1-benzopyran-3-yl)-1,3-dihydro-5-(2-((phenylmethyl)amino)ethyl)-2H-imidazole-2-thione

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A 250 L reactor was charged with 12.25 kg of (R)-5-(2-aminoethyl)-1-(6,8-difluorochroman-3-yl)-1H-imidazole-2(3H)-thione hydrochloride, 114.82 kg of 2-propanol was added and the mixture was stirred at maximum speed (140 rpm). Through a dropping funnel 1.856 kg of benzaldehyde was added followed by 3.945 kg of sodium triacetoxyborohydride in five portions at Ti=20-25° C. according to the following addition order:

Workup

  1. additionwas added
  2. additionaccording to the following addition order

Sources & evidence

ORD record
ord-742353cd3176484d98ed97b7327c21dd
Source dataset
uspto-grants-2014_10
Patent number
US08865913B2

Reaction notes

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