Triethylamine → (S)-4-(7-(3-methoxy-5-(2-methylpyrrolidin-1-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzamide

HRID 1410113Notes

Reaction equation

HRID 1410113 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:15][C:16]2[C:17]3[N:33]=[CH:32][S:31][C:18]=3[N:19]=[C:20]([C:22]3[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][CH:23]=3)[N:21]=2)[CH:6]=[C:7]([N:9]2[CH2:13][CH2:12][CH2:11][C@@H:10]2[CH3:14])[CH:8]=1.CC[N:36]=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(CC)CC>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:15][C:16]2[C:17]3[N:33]=[CH:32][S:31][C:18]=3[N:19]=[C:20]([C:22]3[CH:30]=[CH:29][C:25]([C:26]([NH2:36])=[O:27])=[CH:24][CH:23]=3)[N:21]=2)[CH:6]=[C:7]([N:9]2[CH2:13][CH2:12][CH2:11][C@@H:10]2[CH3:14])[CH:8]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 68379519(S)-4-(7-(3-methoxy-5-(2-methylpyrrolidin-1-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoic acid

Product 1

HCID 66550344(S)-4-(7-(3-methoxy-5-(2-methylpyrrolidin-1-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzamideYield 10%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The mixture of (S)-4-(7-(3-methoxy-5-(2-methylpyrrolidin-1-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoic acid, EDCI (56 mg, 0.29 mmol), HOBt (39 mg, 0.29 mmol) and Et3N (39 mg, 0.39 mmol) in DCM (20 mL) was stirred at room temperature for 3 hrs, then ammonia was bubbled into this mixture for 3 h. The mixture was filtered and the filtrate was concentrated to give a residue which was purified by column chromatography (DCM:MeOH=50:1) to afford (S)-4-(7-(3-methoxy-5-(2-methylpyrrolidin-1-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzamide (12 mg, 10%) as yellow solid. 1H NMR (300 MHz, DMSO): δ 9.99 (s, 1H), 9.40 (s, 1H), 8.49 (s, 1H), 8.46 (s, 1H), 8.12 (s, 1H), 8.01 (s, 1H), 7.98 (s, 1H), 7.49 (s, 1H), 7.15 (s, 1H), 7.05 (s, 1H), 5.88 (s, 1H), 3.93-3.90 (m, 1H), 3.79 (s, 3H), 3.43-3.40 (m, 1H), 3.18-3.15 (m, 1H), 2.06-1.98 (m, 3H), 1.69 (s, 1H), 1.15 (d, 3H, J=6.0 Hz). LC-MS: 461 [M+H]+, tR=1.6 min. HPLC: 95.06% at 214 nm, 95.01% at 254 nm, tR=5.55 min.

Workup

  1. customammonia was bubbled into this mixture for 3 h
  2. filtrationThe mixture was filtered
  3. concentrationthe filtrate was concentrated
  4. customto give a residue which
  5. customwas purified by column chromatography (DCM:MeOH=50:1)

Sources & evidence

ORD record
ord-6a9824ec91f847e39d2ac4009afd3a59
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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