Triethylamine → HCID 58367248, compound

HRID 1891490Notes

Reaction equation

HRID 1891490 reaction equation
C1N=CN(C(N2C=NC=C2)=[O:7])C=1.Cl.[NH2:14][C@H:15]1[C:23]2[C:18](=[C:19]([C:24]3[S:25][C:26]([C:29]4[CH:30]=[CH:31][C:32]([O:37][CH:38]([CH3:40])[CH3:39])=[C:33]([CH:36]=4)[C:34]#[N:35])=CN=3)[CH:20]=[CH:21][CH:22]=2)[CH2:17][CH2:16]1.C[CH2:42][N:43]([CH2:46][CH3:47])[CH2:44][CH3:45].[NH:48]1[CH2:52]CCC1>C(Cl)Cl>[C:34]([C:33]1[CH:36]=[C:29]([C:26]2[S:25][C:24]([C:19]3[CH:20]=[CH:21][CH:22]=[C:23]4[C:18]=3[CH2:17][CH2:16][C@H:15]4[NH:14][C:42]([N:43]3[CH2:46][CH2:47][CH2:45][CH2:44]3)=[O:7])=[CH:52][N:48]=2)[CH:30]=[CH:31][C:32]=1[O:37][CH:38]([CH3:39])[CH3:40])#[N:35]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 31268PyrrolidineHCID 682631,1'-CarbonyldiimidazoleHCID 67196322HCID 67196322, compound

Product 1

HCID 58367248HCID 58367248, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Prepared using General Procedure 19: To CDI (117 mg, 0.72 mmol) in DCM (1 mL) was added a suspension of (R)-5-(5-(1-amino-2,3-dihydro-1H-inden-4-yl)thiazol-2-yl)-2-isopropoxybenzonitrile hydrochloride 72 (150 mg, 0.36 mmol), Et3N (145 mg, 1.44 mmol) and DCM (1 mL) and the mixture stirred for 2 h at room temperature. The resulting solution was added to the preparative solution of pyrrolidine (77 mg, 1.08 mmol)) at room temperature. The reaction was stirred at room temperature for 16 h. The solvent was evaporated and the crude material was purified by preparative HPLC to afford 110 mg of (78%) of (R)-N-(4-(2-(3-cyano-4-isopropoxyphenyl)thiazol-5-yl)-2,3-dihydro-1H-inden-1-yl)pyrrolidine-1-carboxamide 172. LCMS-ESI (m/z) calculated for C27H28N4O2S: 472.1; found 473.2 [M+H]+, tR=3.79 min. 1H NMR (400 MHz, DMSO) δ 8.28 (d, J=2.3 Hz, 1H), 8.22 (dd, J=8.9, 2.4 Hz, 1H), 8.15 (s, 1H), 7.53 (d, J=7.3 Hz, 1H), 7.44 (d, J=9.1 Hz, 1H), 7.36-7.24 (m, 2H), 6.42 (d, J=8.6 Hz, 1H), 5.29 (q, J=8.4 Hz, 1H), 4.91 (hept, J=5.9 Hz, 1H), 3.31-3.20 (m, 4H), 3.17-2.95 (m, 2H), 2.43 (ddd, J=10.7, 6.2, 2.8 Hz, 1H), 2.00-1.87 (m, 1H), 1.87-1.72 (m, 4H), 1.37 (d, J=6.0 Hz, 6H); 13 C NMR (101 MHz, CDCl3) δ 164.79, 160.90, 156.46, 146.16, 141.10, 140.75, 137.75, 131.89, 131.80, 127.75, 127.71, 127.63, 126.53, 124.27, 115.92, 113.78, 103.60, 72.34, 55.78, 45.61, 34.87, 30.80, 25.57, 21.81.

Workup

  1. customPrepared
  2. stirringThe reaction was stirred at room temperature for 16 h
  3. customThe solvent was evaporated
  4. customthe crude material was purified by preparative HPLC

Sources & evidence

ORD record
ord-d9ee71c6a1a84754a4128aa2867fb231
Source dataset
uspto-grants-2013_08
Patent number
US08507538B2

Reaction notes

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