2-Chloroethanol → HCID 135410965, compound

HRID 601405Notes

Reaction equation

HRID 601405 reaction equation
Cl[S:2]([N:5]=[C:6]=[O:7])(=[O:4])=[O:3].[Cl:8][CH2:9][CH2:10][OH:11].[NH2:12][C:13]1[CH:41]=[CH:40][C:16]2[NH:17][C:18]([C:23]3[C:24](=[O:39])[N:25]([CH2:34][CH2:35][CH:36]([CH3:38])[CH3:37])[C:26]4[C:31]([C:32]=3[OH:33])=[CH:30][CH:29]=[CH:28][N:27]=4)=[N:19][S:20](=[O:22])(=[O:21])[C:15]=2[CH:14]=1.C(N(CC)CC)C.Cl>ClCCl>[OH:33][C:32]1[C:31]2[C:26](=[N:27][CH:28]=[CH:29][CH:30]=2)[N:25]([CH2:34][CH2:35][CH:36]([CH3:37])[CH3:38])[C:24](=[O:39])[C:23]=1[C:18]1[NH:17][C:16]2[CH:40]=[CH:41][C:13]([NH:12][S:2]([NH:5][C:6](=[O:7])[O:11][CH2:10][CH2:9][Cl:8])(=[O:4])=[O:3])=[CH:14][C:15]=2[S:20](=[O:21])(=[O:22])[N:19]=1

Participants

7

Reactant 5

HCID 342-ChloroethanolHCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 70918Chlorosulfonyl isocyanateHCID 1354307103-(7-Amino-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-1-(3-methylbutyl)-1,8-naphthyridin-2(1H)-one

Product 1

HCID 135410965HCID 135410965, compoundYield 68.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution of chlorosulfonyl isocyanate (33 mg, 0.23 mmol) in dichloromethane (8 mL) was cooled to 0° C. and 2-chloroethanol (18.8 mg, 0.23 mmol) was added dropwise. The mixture was stirred at 0° C. for 90 minutes followed by the addition of a solution containing the product of Example 205 (100 mg, 0.23 mmol) and triethylamine (71 mg, 0.70 mmol) in dichloromethane (2 mL). The mixture was stirred for 24 hrs at 25° C. then partititioned between dichloromethane (25 mL) and 1N aqueous hydrochloric acid (20 mL). The resulting organic layer was separated and dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide the title compound (96 mg, 67%). MS (ESI−) m/z 611 (M−H)−. 1H NMR (300 MHz, DMSO-d6) δ 0.98 (d, J=6.62 Hz, 6 H) 1.57 (m, 2 H) 1.69 (m, 1 H) 3.78 (m, 2 H) 4.32 (m, 2 H) 4.49 (m, 2 H) 7.51 (m, 2 H) 7.63 (s, 1 H) 7.77 (d, J=9.19 Hz, 1 H) 8.56 (dd, J=7.72, 1.10 Hz, 1 H) 8.90 (dd, J=4.41, 1.47 Hz, 1 H) 11.15 (s, 1 H) 12.26 (s, 1 H) 14.10 (s, 1 H).

Workup

  1. additionfollowed by the addition of a solution
  2. stirringThe mixture was stirred for 24 hrs at 25° C.
  3. customThe resulting organic layer was separated
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f6bcdcbcb72b4cf79ee5d37b9e7f4537
Source dataset
uspto-grants-2011_03
Patent number
US07902203B2

Reaction notes

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