Sodium hydride → 2-[8-(Benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1H-isoquinolin-2-yl]-5-{3-[4-(4-cyano-thiophen-3-yl)-phenoxy]-propyl]-thiazole-4-carboxylic acid

HRID 1518329Notes

Reaction equation

HRID 1518329 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([C:13]#[N:14])=[CH:10][S:11][CH:12]=2)=[CH:4][CH:3]=1.[H-].[Na+].[S:17]1[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=2[N:19]=[C:18]1[NH:26][C:27]([C:29]1[CH:30]=[CH:31][CH:32]=[C:33]2[C:38]=1[CH2:37][N:36]([C:39]1[S:40][C:41]([CH2:49][CH2:50][CH2:51]I)=[C:42]([C:44]([O:46]CC)=[O:45])[N:43]=1)[CH2:35][CH2:34]2)=[O:28]>CN(C=O)C>[S:17]1[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=2[N:19]=[C:18]1[NH:26][C:27]([C:29]1[CH:30]=[CH:31][CH:32]=[C:33]2[C:38]=1[CH2:37][N:36]([C:39]1[S:40][C:41]([CH2:49][CH2:50][CH2:51][O:1][C:2]3[CH:3]=[CH:4][C:5]([C:8]4[C:9]([C:13]#[N:14])=[CH:10][S:11][CH:12]=4)=[CH:6][CH:7]=3)=[C:42]([C:44]([OH:46])=[O:45])[N:43]=1)[CH2:35][CH2:34]2)=[O:28]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 59447467ethyl 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-iodopropyl)thiazole-4-carboxylateHCID 594475724-(4-Hydroxyphenyl)thiophene-3-carbonitrile

Product 1

HCID 468362452-[8-(Benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1H-isoquinolin-2-yl]-5-{3-[4-(4-cyano-thiophen-3-yl)-phenoxy]-propyl]-thiazole-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To compound 51A (0.095 g, 0.015 mmol) in DMF (4 mL) was added 60% sodium hydride (0.036 g, 0.9 mmol) at 0° C. The solution was stirred for 10 minutes. To this solution was added compound 2C. The solution was stirred at rt for 2 hours. The reaction was quenched with MeOH (1 mL). Conc. HCl (0.5 mL) was added, and the solution was filtered through a syringe filter. The filtrate was then purified by Prep HPLC to provide the desired product 51: 1H NMR (DMSO-d6): δ 8.57 (d, J=3.38 Hz, 1H), 7.95 (d, J=7.98 Hz, 1H), 7.71-7.72 (m, 2H), 7.60 (d, J=7.36 Hz, 1H), 7.45-7.48 (m, 2H), 7.26-7.41 (m, 4H), 6.95-6.97 (m, 214), 4.77 (s, 2H), 3.97 (t, J=6.29 Hz, 2H), 3.66 (t, J=5.98 Hz, 2H), 3.11-3.14 (m, 2H), 2.96 (t, J=5.98 Hz, 2H), 1.93-2.00 (m, 2H); MS (ESI(+)): m/z 678 (M+H).

Workup

  1. stirringThe solution was stirred at rt for 2 hours
  2. customThe reaction was quenched with MeOH (1 mL)
  3. additionConc. HCl (0.5 mL) was added
  4. filtrationthe solution was filtered through a syringe
  5. filtrationfilter
  6. customThe filtrate was then purified by Prep HPLC

Sources & evidence

ORD record
ord-20bd72b11caa4eb5a7d832641dee7d76
Source dataset
uspto-grants-2012_07
Patent number
US08232273B2

Reaction notes

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