Acetic Acid → HCID 53467175, compound

HRID 1909952Notes

Reaction equation

HRID 1909952 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[NH2:15][C:16]1[C:21]2[C:22]([C:25]3[CH:26]=[C:27]4[C:31](=[CH:32][CH:33]=3)[N:30]([C:34](=[O:42])[CH2:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[CH2:29][CH2:28]4)=[CH:23][S:24][C:20]=2[C:19]([C:43]2[CH:44]=[C:45]([CH:48]=[CH:49][CH:50]=2)[CH:46]=O)=[CH:18][N:17]=1.[CH3:51][NH:52][CH3:53].C1COCC1.CC(O)=O>ClCCCl>[CH3:51][N:52]([CH2:46][C:45]1[CH:44]=[C:43]([C:19]2[C:20]3[S:24][CH:23]=[C:22]([C:25]4[CH:26]=[C:27]5[C:31](=[CH:32][CH:33]=4)[N:30]([C:34](=[O:42])[CH2:35][C:36]4[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=4)[CH2:29][CH2:28]5)[C:21]=3[C:16]([NH2:15])=[N:17][CH:18]=2)[CH:50]=[CH:49][CH:48]=1)[CH3:53]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 674Dimethylamine2×HCID 8028Tetrahydrofuran2×HCID 5049666Sodium triacetoxyborohydride2×HCID 86663679HCID 86663679, compound

Product 1

HCID 53467175HCID 53467175, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Sodium triacetoxyborohydride (76 mg, 0.359 mmol) was added to a solution of 3-{4-amino-3-[1-(phenylacetyl)-2,3-dihydro-1H-indol-5-yl]thieno[3,2-c]pyridin-7-yl}benzaldehyde (66 mg, 0.135 mmol), dimethylamine, 2.0 M in THF (0.10 mL, 0.200 mmol), and acetic acid (8 μL, 0.140 mmol) in 1,2-Dichloroethane (DCE) (7 mL), and the mixture was stirred at room temperature under Nitrogen for 3 days. LCMS showed only starting material, so another portion each of dimethylamine, 2.0 M in THF (0.20 mL, 0.400 mmol) and sodium triacetoxyborohydride (162 mg, 0.764 mmol) were added. Stirring continued at room temperature for another 3.5 hr, when LCMS showed complete conversion to the desired product. The mixture was poured into saturated aqueous NaHCO3 (15 mL) and extracted with methylene chloride (2×15 mL). The extracts were dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by reverse phase HPLC (Gilson, C18, 5% to 45% CH3CN in water with 0.1% TFA, 8 minute gradient). The product fractions were combined and concentrated in vacuo, and the residue was taken up in MeOH and passed through a PL-HCO3 MP-resin cartridge, rinsing with more MeOH. The filtrate was concentrated in vacuo and dried in the vacuum oven overnight to give 7-{3-[(dimethylamino)methyl]phenyl}-3-[1-(phenylacetyl)-2,3-dihydro-1H-indol-5-yl]thieno[3,2-c]pyridin-4-amine (50 mg, 0.092 mmol, 67.9% yield) as a white solid. LC/MS (ES) m/z=519 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 2.20 (s, 6H), 3.24 (t, J=8.34 Hz, 2H), 3.47 (s, 2H), 3.90 (s, 2H), 4.26 (t, J=8.46 Hz, 2H), 5.53 (br. s., 2H), 7.23-7.30 (m, 2H), 7.30-7.39 (m, 6H), 7.43-7.50 (m, 2H), 7.51-7.56 (m, 1H), 7.60 (s, 1H), 7.90 (s, 1H), 8.18 (d, J=8.34 Hz, 1H).

Sources & evidence

ORD record
ord-86c78369d38f4d72a461f27bf5818ef8
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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