Hydrochloric Acid → HCID 86695098, compound

HRID 1503921Notes

Reaction equation

HRID 1503921 reaction equation
[ClH:1].[C:2]([CH2:5][NH:6][C:7]([CH2:9][C@H:10]1[CH2:21][CH2:20][C:19]2[S:18][C:17]3[N:16]=[CH:15][N:14]=[C:13]([O:22][CH:23]4[CH2:28][CH2:27][CH:26]([N:29](C)[C:30](=O)OC(C)(C)C)[CH2:25][CH2:24]4)[C:12]=3[C:11]1=2)=[O:8])(=[O:4])[NH2:3]>C(Cl)Cl>[ClH:1].[C:2]([CH2:5][NH:6][C:7](=[O:8])[CH2:9][C@H:10]1[CH2:21][CH2:20][C:19]2[S:18][C:17]3[N:16]=[CH:15][N:14]=[C:13]([O:22][CH:23]4[CH2:24][CH2:25][CH:26]([NH:29][CH3:30])[CH2:27][CH2:28]4)[C:12]=3[C:11]1=2)(=[O:4])[NH2:3]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86695097HCID 86695097, compound

Product 1

HCID 86695098HCID 86695098, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

HCl (gas) was introduced into DCM (50 mL) at 0° C. for 30 min with stirring. Then a solution of tert-butyl N-(4-[[(3R)-3-[[(carbamoylmethyl)carbamoyl]methyl]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)-N-methylcarbamate (140 mg, 0.27 mmol, 1.00 equiv) in 5 mL of DCM was added and the resulting solution was stirred overnight at room temperature. The solvent was removed under vacuum to provide 120 mg of N-(carbamoylmethyl)-2-[(3R)-12-[[4-(methylamino)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]acetamide hydrochloride as a yellow solid. The solid was dissolved in methanol (10 mL) and HCHO (37%, 0.5 mL) and acetic acid (0.5 mL) were added at room temperature. After stirring for 20 min at room temperature, NaBH3CN (100 mg) was added and the resulting mixture was stirred for 1 h at ambient temperature. After concentration in vacuo, the residue was purified by preparative HPLC under the following conditions (Waters): column: X-briage C18, 19*150 mm 5 um; mobile phase: CH3CN and water with 20 mM NH4HCO3 (10.0% CH3CN up to 50.0% in 10 min, up to 95% in 2 min, down to 10.0% in 2 min); flow rate: 20 mL/min; UV detection at 254/220 nm. The product-containing fractions were collected and partially evaporated to remove water and CH3CN under reduced pressure. The residue was lyophilized overnight to give the desired N-(2-amino-2-oxoethyl)-2-((R)-4-(((1r,4R)-4-(dimethylamino)cyclohexyl)oxy)-6,7-dihydro-SH-cyclopenta[4,5]thieno[2,3-d]pyrimidin-5-yl)acetamide (154.3 mg, 71%) as a white solid. MS: m/z 432 [M+H]+, 454 [M+Na]+; 1H NMR (400 MHz, CD3OD): δ 8.47 (1H, s), 5.28-5.23 (1H, m), 3.89 (2H, s), 3.86-3.77 (1H, m), 3.15-2.99 (3H, m), 2.74-2.68 (1H, m), 2.44-2.34 (11H, m), 2.06-2.04 (2H, m), 1.73-1.58 (2H, m), 1.57-1.43 (2H, m).

Workup

  1. stirringthe resulting solution was stirred overnight at room temperature
  2. customThe solvent was removed under vacuum

Sources & evidence

ORD record
ord-375e0b96cfb94483b5450d5cf8377020
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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