Sodium Hydroxide → HCID 90279805, compound

HRID 510814Notes

Reaction equation

HRID 510814 reaction equation
[CH3:1][CH2:2][N:3]1[C:7]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=2)=[C:6]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([N:21]3[CH2:26][CH2:25][N:24]([C:27]4[CH:32]=[CH:31][C:30]([NH:33][S:34]([C:37]5[CH:42]=[CH:41][C:40]([NH:43][C@@H:44]([CH2:54][S:55][C:56]6[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=6)[CH2:45][CH2:46][N:47]6[CH2:52][CH2:51][CH:50]([OH:53])[CH2:49][CH2:48]6)=[C:39]([S:62]([C:65]([F:68])([F:67])[F:66])(=[O:64])=[O:63])[CH:38]=5)(=[O:36])=[O:35])=[CH:29][CH:28]=4)[CH2:23][CH2:22]3)[CH:16]=2)[C:5]([C:69]([OH:71])=O)=[C:4]1[CH3:72].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[NH2:94][CH:95]1[CH2:100][CH2:99][CH:98]([C:101]([O:103]C)=[O:102])[CH2:97][CH2:96]1.[OH-].[Na+]>C(Cl)Cl.C(OCC)(=O)C>[Cl:14][C:11]1[CH:10]=[CH:9][C:8]([C:7]2[N:3]([CH2:2][CH3:1])[C:4]([CH3:72])=[C:5]([C:69]([NH:94][CH:95]3[CH2:100][CH2:99][CH:98]([C:101]([OH:103])=[O:102])[CH2:97][CH2:96]3)=[O:71])[C:6]=2[C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([N:21]3[CH2:26][CH2:25][N:24]([C:27]4[CH:32]=[CH:31][C:30]([NH:33][S:34]([C:37]5[CH:42]=[CH:41][C:40]([NH:43][C@H:44]([CH2:45][CH2:46][N:47]6[CH2:52][CH2:51][CH:50]([OH:53])[CH2:49][CH2:48]6)[CH2:54][S:55][C:56]6[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=6)=[C:39]([S:62]([C:65]([F:68])([F:66])[F:67])(=[O:63])=[O:64])[CH:38]=5)(=[O:35])=[O:36])=[CH:29][CH:28]=4)[CH2:23][CH2:22]3)[CH:16]=2)=[CH:13][CH:12]=1

Participants

8

Reactant 5

HCID 14798Sodium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 422580Methyl 4-aminocyclohexanecarboxylateHCID 714569955-(4-chlorophenyl)-1-ethyl-4-[3-[4-[4-[[4-[[(2R)-4-(4-hydroxypiperidin-1-yl)-1-phenylsulfanylbutan-2-yl]amino]-3-(trifluoromethylsulfonyl)phenyl]sulfonylamino]phenyl]piperazin-1-yl]phenyl]-2-methylpyrrole-3-carboxylic acid2×

Product 1

HCID 90279805HCID 90279805, compoundYield 56.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of BM-957 (100 mg, 0.09 mmol), EDCI (27 mg, 0.14 mmol) and HOBT (19 mg, 0.14 mmol) in DCM (2 mL) was added methyl 4-aminocyclohexanecarboxylate (44 mg, 0.28 mmol). The solution was stirred for 2 hours at room temperature until no BM-957 was observed by TLC. The reaction mixture was diluted with ethyl acetate (50 mL), washed with saturated NaHCO3 solution (50 mL), brine (50 mL) and dried over sodium sulfate. The solvent was removed in vacuo to give crude product which was used for next step without purification. The resulting residue was dissolved in H2O and MeOH (5 mL and 5 mL respectively) and followed by adding NaOH (76 mg, 1.9 mmol). The solution was stirred at room temperature for 20 h until no starting material was observed by TLC. The reaction mixture was concentrated in vacuo and the residue was purified by HPLC to give the pure product 10 (salt with TFA, 61 mg, yield 55% over two steps). The gradient ran from 60% of solvent A and 40% of solvent B to 20% of solvent A and 80% of solvent B in 40 min. MS (ESI): m/z 1191.17 (M+H)+.

Workup

  1. washwashed with saturated NaHCO3 solution (50 mL), brine (50 mL)
  2. dry with materialdried over sodium sulfate
  3. customThe solvent was removed in vacuo
  4. customto give crude product which
  5. customwas used for next step without purification
  6. dissolutionThe resulting residue was dissolved in H2O
  7. concentrationThe reaction mixture was concentrated in vacuo
  8. customthe residue was purified by HPLC

Sources & evidence

ORD record
ord-fc2756004494450d9b90e26cae224dac
Source dataset
uspto-grants-2015_08
Patent number
US09096625B2

Reaction notes

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