1,2-Dichloroethane → HCID 57812413, compound

HRID 912010Notes

Reaction equation

HRID 912010 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([Cl:9])[C:3]=1[C@H:10]([O:12][C:13]1[C:14]2[O:22][CH:21]=[C:20]([C:23]3[CH2:24][CH2:25][NH:26][CH2:27][CH:28]=3)[C:15]=2[CH:16]=[N:17][C:18]=1[NH2:19])[CH3:11].O=[C:30]1[CH2:33][N:32](C(OC(C)(C)C)=O)[CH2:31]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].ClCCCl.C(Cl)Cl.C(O)(C(F)(F)F)=O>>[NH:32]1[CH2:33][CH:30]([N:26]2[CH2:25][CH:24]=[C:23]([C:20]3[C:15]4[CH:16]=[N:17][C:18]([NH2:19])=[C:13]([O:12][C@@H:10]([C:3]5[C:4]([Cl:9])=[CH:5][CH:6]=[C:7]([F:8])[C:2]=5[Cl:1])[CH3:11])[C:14]=4[O:22][CH:21]=3)[CH2:28][CH2:27]2)[CH2:31]1

Participants

7

Reactant 6

HCID 111,2-DichloroethaneHCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl esterHCID 5049666Sodium triacetoxyborohydrideHCID 57812480HCID 57812480, compound

Product 1

HCID 57812413HCID 57812413, compound

Conditions

Temperature
70 °C

Procedure

7-[(R)-1-(2,6-Dichloro-3-fluorophenyl)ethoxy]-3-(1,2,3,6-tetrahydropyridin-4-yl)furo[3,2-c]pyridin-6-ylamine (10.0 mg, 0.0237 mmol), tert-butyl 3-oxoazetidine-1-carboxylate (8.11 mg, 0.0474 mmol), sodium triacetoxyborohydride (25.1 mg, 0.118 mmol) and 1,2-dichloroethane (1.0 mL, 13 mmol) were mixed and stirred at 70° C. overnight. After extraction with DCM and water, the organic layer was dried and dissolved in DCM (1.0 mL, 16 mmol). TFA (1.0 mL, 13 mmol) was added at 0° C. The mixture was stirred at 0° C. for 1 hour. The crude was passed through SCX-2 SPE and product was released by 2 M NH3 in methanol for purification by the MDPS. MS (ES+): m/z 477.10/479.15 (100/80) [MH+]. HPLC: tR=0.57 min (HPLC-ACQUITY, Analytical). 1H NMR (400 MHz, CD3OD): δ=1.88 (d, J=6.8 Hz, 3H), 2.54 (br. s., 2H), 2.64-2.68 (m, 2H), 3.11-3.18 (m, 2H), 3.53 (t, J=6.9 Hz, 1H), 3.94-4.08 (m, 4H), 6.27 (br. s., 1H), 6.50 (q, J=7.0 Hz, 1H), 7.22 (t, J=8.6 Hz, 1H), 7.40 (dd, J=9.0, 4.9 Hz, 1H), 7.63 (s, 1H), 8.18 (s, 1H).

Workup

  1. extractionAfter extraction with DCM and water
  2. customthe organic layer was dried
  3. stirringThe mixture was stirred at 0° C. for 1 hour
  4. customwas released by 2 M NH3 in methanol for purification by the MDPS

Sources & evidence

ORD record
ord-15442cea2cc54ec4b7747426d57229a3
Source dataset
uspto-grants-2011_09
Patent number
US08022206B2

Reaction notes

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