Acetic Acid → 1-(4-(6-Benzylbenzo[d]thiazol-2-yl)-3-fluorobenzyl)azetidine-3-carboxylic acid

HRID 2075267Notes

Reaction equation

HRID 2075267 reaction equation
[CH2:1]([C:8]1[CH:25]=[CH:24][C:11]2[N:12]=[C:13]([C:15]3[CH:22]=[CH:21][C:18]([CH:19]=O)=[CH:17][C:16]=3[F:23])[S:14][C:10]=2[CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:26]1[CH2:29][CH:28]([C:30]([OH:32])=[O:31])[CH2:27]1.C(O)(=O)C.[Na]>CO.C(Cl)Cl>[CH2:1]([C:8]1[CH:25]=[CH:24][C:11]2[N:12]=[C:13]([C:15]3[CH:22]=[CH:21][C:18]([CH2:19][N:26]4[CH2:29][CH:28]([C:30]([OH:32])=[O:31])[CH2:27]4)=[CH:17][C:16]=3[F:23])[S:14][C:10]=2[CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 931923-azetidinecarboxylic AcidHCID 5360545SodiumHCID 584152504-(6-Benzylbenzo[d]thiazol-2-yl)-3-fluorobenzaldehyde

Product 1

HCID 533247461-(4-(6-Benzylbenzo[d]thiazol-2-yl)-3-fluorobenzyl)azetidine-3-carboxylic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

At 24° C., a mixture of 4-(6-benzylbenzo[d]thiazol-2-yl)-3-fluorobenzaldehyde (190 mg, 547 μmol), azetidine-3-carboxylic acid (166 mg, 1641 μmol), acetic acid (0.095 mL, 1641 μmol) in MeOH (2 mL) and DCM (2 mL) was stirred for 1 h. The light yellow solution was treated with sodium borocyanohydride (34 mg, 547 μmol). The mixture was stirred for 12 h. The solids were filtered off and washed 3× with DCM, suspended in 4 mL of an aqueous buffered solution (phosphate buffer pH 6) and sonicated for 10 min. The mixture was filtered and the solids washed with water and dried in vacuo to yield 1-((4-(6-Benzylbenzo[d]thiazol-2-yl)-3-fluorophenyl)methyl)azetidine-3-carboxylic acid as a white solid [hS1P1 EC50=149 nM]. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.27 (t, J=8.4 Hz, 1H), 8.04 (s, 1H), 8.01 (d, J=8.4 Hz, 1H), 7.44 (d, J=6.6 Hz, 1H), 7.34-7.29 (m, 6H), 7.21-7.20 (m, 1H), 4.11 (s, 2H), 3.83-3.82 (br. m, 1H), 3.63 (s, 2H), 3.41 (t, J=6.8 Hz, 2H), 3.21 (t, J=7.0 Hz, 2H). MS (ESI) m/z: Calculated: 432.5; Observed: 433.2 (M++1).

Workup

  1. stirringThe mixture was stirred for 12 h
  2. filtrationThe solids were filtered off
  3. washwashed 3× with DCM
  4. customsonicated for 10 min
  5. filtrationThe mixture was filtered
  6. washthe solids washed with water
  7. customdried in vacuo

Sources & evidence

ORD record
ord-bca1adcf923d45aeb43d48aa055318b3
Source dataset
uspto-grants-2011_04
Patent number
US07919519B2

Reaction notes

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