[ CAS No. 45434-02-4 ] {[proInfo.proName]}

Name: 45434-02-4|(1-(Aminomethyl)cyclopropyl)methanol|98%
Brand: Ambeed
SKU: A355027
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Quality Control of [ 45434-02-4 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 45434-02-4 ]

SDS Specification

Alternatived Products of [ 45434-02-4 ]

Product Details of [ 45434-02-4 ]

CAS No. :	45434-02-4	MDL No. :	MFCD09864388
Formula :	C₅H₁₁NO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	KTBPXPGXDDKAGN-UHFFFAOYSA-N
M.W :	101.15	Pubchem ID :	22379495
Synonyms :

Calculated chemistry of [ 45434-02-4 ]

Physicochemical Properties

Num. heavy atoms :	7
Num. arom. heavy atoms :	0
Fraction Csp3 :	1.0
Num. rotatable bonds :	2
Num. H-bond acceptors :	2.0
Num. H-bond donors :	2.0
Molar Refractivity :	27.64
TPSA :	46.25 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.48 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.24
Log Po/w (XLOGP3) :	-0.8
Log Po/w (WLOGP) :	-0.35
Log Po/w (MLOGP) :	-0.16
Log Po/w (SILICOS-IT) :	0.46
Consensus Log Po/w :	0.08

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	0.17
Solubility :	149.0 mg/ml ; 1.48 mol/l
Class :	Highly soluble
Log S (Ali) :	0.31
Solubility :	205.0 mg/ml ; 2.03 mol/l
Class :	Highly soluble
Log S (SILICOS-IT) :	-0.5
Solubility :	32.2 mg/ml ; 0.318 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.0

Safety of [ 45434-02-4 ]

Signal Word:	Danger	Class:	3,8
Precautionary Statements:	P210-P261-P280-P305+P351+P338-P310	UN#:	2924
Hazard Statements:	H225-H302-H314-H335-H413	Packing Group:	Ⅲ
GHS Pictogram:

Application In Synthesis of [ 45434-02-4 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Downstream synthetic route of [ 45434-02-4 ]

[ 45434-02-4 ] Synthesis Path-Downstream 1~65

1
[ 50-00-0 ]
[ 45434-02-4 ]
[ 39943-41-4 ]

Yield	Reaction Conditions	Operation in experiment
27%	Stage #1: formaldehyd; (1-(aminomethyl)cyclopropyl)methanol With acetic acid In methanol at 20℃; for 0.5h; Stage #2: With sodium cyanoborohydride In methanol at 0 - 20℃;	Intermediate 10 Preparation of (1-((dimethylamino)methyl)cyclopropyl)methanol Combine (1-(aminomethyl)cyclopropyl)methanol (800mg, 7.92mmol), paraformaldehyde (1.43g, 47.52mmol)And acetic acid (48mg, 0.8mmol) was added to methanol (10mL) and stirred at room temperature for half an hour.The reaction solution was cooled to zero, and sodium cyanoborohydride (3.0 g, 47.52 mmol) was slowly added. The reaction solution was stirred at room temperature overnight. TLC showed that a new spot appeared.The reaction solution was concentrated to remove methanol to obtain a crude product. The crude product was diluted with saturated potassium carbonate solution and extracted with ethyl acetate 3 times.The combined organic phases were dried, concentrated, and passed through a silica gel column (eluent: dichloromethane/methanol=10/1) to obtain the target product (273 mg), yield: 27%.
	With formic acid

Reference： [1]Current Patent Assignee: SUZHOU ZELGEN BIOPHARMACEUTICAL CO LTD; SHANGHAI ZELGEN PHARMA TECH - CN112694475, 2021, A Location in patent: Paragraph 0317-0321
[2]Newman; Broger; LaPidus; Tye [Journal of medicinal chemistry, 1972, vol. 15, # 10, p. 1003 - 1006]

2
[ 1558-81-2 ]
[ 45434-02-4 ]

Reference： [1]Journal of medicinal chemistry,1972,vol. 15,p. 1003 - 1006
[2]Russian Chemical Bulletin,2014,vol. 63,p. 409 - 415
Izvestiya Akademii Nauk. Seriya Khimicheskaya,2014,vol. 2,p. 409 - 415,7

3
[ 6914-80-3 ]
[ 45434-02-4 ]

Yield	Reaction Conditions	Operation in experiment
79.6%	With lithium aluminium tetrahydride In tetrahydrofuran for 6h;
	With lithium aluminium tetrahydride In tetrahydrofuran

Reference： [1]Buchholz, Mirko; Heiser, Ulrich; Schilling, Stephan; Niestroj, André J.; Zunkel, Katrin; Demuth, Hans-Ulrich [Journal of Medicinal Chemistry, 2006, vol. 49, # 2, p. 664 - 677]
[2]Chan, Kelvin S. L.; Fu, Hai-Yan; Yu, Jin-Quan [Journal of the American Chemical Society, 2015, vol. 137, # 5, p. 2042 - 2046]

4
[ 24424-99-5 ]
[ 45434-02-4 ]
[ 153248-46-5 ]

Yield	Reaction Conditions	Operation in experiment
		Step 2: Synthesis of tert-butyl [l-(hydroxymethyl)cyclopropyl]methyl}carbamate Di-tert-butyl dicarbonate (40.5 mL, 197 mmol) is added to a stirred solution of [1- (aminomethyl)cyclopropyl]methanol (20 g, 198 mmol) in CH2C12 (600 mL) at room temperature. The reaction mixture is stirred at same temperature for 40 h. Then saturated NH4C1 solution (250 mL) is added and the reaction mixture is stirred for another 10 min. The organic layer is separated, washed with saturated NaHC03 solution (100 mL), dried (Na2S04) and concentrated to afford the title compound (20 g, 56 % for 2 steps) as a white solid.

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 664 - 677
[2]Patent: WO2011/71716,2011,A1 .Location in patent: Page/Page column 76-77

5
[ 45434-02-4 ]
[ 36176-31-5 ]
C₁₅H₂₂N₂OS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane at 20℃;

Reference： [1]Kai, Hiroyuki; Morioka, Yasuhide; Tomida, Minoru; Takahashi, Tadashi; Hattori, Maki; Hanasaki, Kohji; Koike, Katsumi; Chiba, Hiroki; Shinohara, Shunji; Kanemasa, Toshiyuki; Iwamoto, Yuka; Takahashi, Kohji; Yamaguchi, Yoshitaka; Baba, Takahiko; Yoshikawa, Takayoshi; Takenaka, Hideyuki [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 14, p. 3925 - 3929]

6
[ 45434-02-4 ]
[ 877204-21-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: 0.28 g / Et₃N / methanol / 12 h / 50 °C 2.1: Et₃N / CH₂Cl₂ / 15 h / 0 - 20 °C 3.1: NaH / dimethylformamide 3.2: 43.5 percent / dimethylformamide / 8 h / 100 °C 4.1: HCl / dioxane / 1 h / 0 °C

Reference： [1]Buchholz, Mirko; Heiser, Ulrich; Schilling, Stephan; Niestroj, André J.; Zunkel, Katrin; Demuth, Hans-Ulrich [Journal of Medicinal Chemistry, 2006, vol. 49, # 2, p. 664 - 677]

7
[ 45434-02-4 ]
[ 877204-20-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: 0.28 g / Et₃N / methanol / 12 h / 50 °C 2.1: Et₃N / CH₂Cl₂ / 15 h / 0 - 20 °C 3.1: NaH / dimethylformamide 3.2: 43.5 percent / dimethylformamide / 8 h / 100 °C

Reference： [1]Buchholz, Mirko; Heiser, Ulrich; Schilling, Stephan; Niestroj, André J.; Zunkel, Katrin; Demuth, Hans-Ulrich [Journal of Medicinal Chemistry, 2006, vol. 49, # 2, p. 664 - 677]

8
[ 45434-02-4 ]
methanesulfonic acid 1-(<i>tert</i>-butoxycarbonylamino-methyl)-cyclopropylmethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 0.28 g / Et₃N / methanol / 12 h / 50 °C 2: Et₃N / CH₂Cl₂ / 15 h / 0 - 20 °C

Reference： [1]Buchholz, Mirko; Heiser, Ulrich; Schilling, Stephan; Niestroj, André J.; Zunkel, Katrin; Demuth, Hans-Ulrich [Journal of Medicinal Chemistry, 2006, vol. 49, # 2, p. 664 - 677]

9
[ 45434-02-4 ]
1-((1-((1H-imidazol-1-yl)methyl)cyclopropyl)methyl)-3-(3,4-dimethoxy-phenyl)thiourea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: 0.28 g / Et₃N / methanol / 12 h / 50 °C 2.1: Et₃N / CH₂Cl₂ / 15 h / 0 - 20 °C 3.1: NaH / dimethylformamide 3.2: 43.5 percent / dimethylformamide / 8 h / 100 °C 4.1: HCl / dioxane / 1 h / 0 °C 5.1: 37.5 percent / ethanol / 2 h / Heating

Reference： [1]Buchholz, Mirko; Heiser, Ulrich; Schilling, Stephan; Niestroj, André J.; Zunkel, Katrin; Demuth, Hans-Ulrich [Journal of Medicinal Chemistry, 2006, vol. 49, # 2, p. 664 - 677]

10
[ 853273-61-7 ]
[ 45434-02-4 ]
[ 853273-62-8 ]

Yield	Reaction Conditions	Operation in experiment
	With acetic acid at 60℃; for 24h;	4.IV.e e) { (1S, 2S,4S)-1-{(S)-2-l4-Fluoro-3-(3-methoxy-propoxy)-benzyl]-3-methyl-butyl}-2- hydroxy-4- [ (1-hydroxymethyl-cyclopropylmethyl)-carbamoyl]-5-methyl-hexyl}- carbamic acid ter-butyl ester ; [ (1 S, 3S)-3- [4-Fluoro-3- (3-methoxy-propoxy)-benzyl]-1- ( (2S, 4S)-4-isopropyl-5-oxo- tetrahydro-furan-2-yl)-4-methyl-pentyl]-carbamic acid tert-butyl ester (100g, 0.19mmol, 1 eq), 3-amino-2, 2-dimethylpropanol (0.3 g, 2.8 mmol, 15 eq) and acetic acid (0.11 uL, 0.002 mmol, 0.01 eq) are stirred at60 C during 24 hours, when the solvent is evaporated. Flash column chromatography(CH2CI2/MeOH 95: 5 to CH2CI2/MeOH 9: 1) affords the product as an light yellow solid. MS (LC-MS): 627[M+H] + ; Rf(CH2CI2/MeOH 9: 1): 0.25. f) (2S, 4S, 5S,7S)-5-Amino-7- [4-fluoro-3- (3-methoxy-propoxy)-benzyl]-4-hydroxy-2- isopropyl-8-methyl-nonanoic acid (1-hydroxymethyl-cyclopropylmethyl)-amide

Reference： [1]Current Patent Assignee: Novartis (w/o Sandoz); NOVARTIS AG - WO2005/51895, 2005, A1 Location in patent: Page/Page column 47-48

11
[ 45434-02-4 ]
[ 13743-09-4 ]
[ 912648-33-0 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; triethylamine; In N,N-dimethyl-formamide; at 150℃; for 0.166667h;Microwave irradiation;	N-{\|"1 -(Hydroxymethypcyclopropylimethyll -2-methyl-5 -phenyl- 1 ,3 -thiazole-4-carboxamide (O-T); A solution of the amino alcohol D2I (0.072 g, 0.709 mmol) in DMF (5 mL)/ Et3N (0.6 mL) was treated with 2-methyl-4-phenyl-thiazolyl-3-carboxylic acid (0.155 g, 0.709 mmol), EDC (0.203 g, 1.06 mmol), and HOBT (0.143 g, 1.06 mmol). The mixture was heated in a microwave reactor for 10 min at 150 0C. After cooling to rt, the mixture was partitioned into water and ethyl acetate, washed with brine, dried, filtered and concentrated. The residue was purified by flash chromatography (SiO2, 100% EtOAc) to provide amide D1I. Data for I>2: 1HNMR (500 MHz, CDCl3) delta 7.88-7.73 (m, IH), 7.60-7.52 (m, 2H), 7.42-7.33(m, 3H), 3.39-3.35 (m, 4H), 2.71 (s, 3H), 0.52-0.48 (m, 4H) ppm.

Reference： [1]Patent: WO2006/110626,2006,A1 .Location in patent: Page/Page column 40

12
[ 45434-02-4 ]
[ 94695-50-8 ]
[ 122-51-0 ]
[ 1132814-84-6 ]

Yield	Reaction Conditions	Operation in experiment
75%		A solution of ethyl 3-oxo-3-(pentafluorophenyl)propionate (7.01 g, 24.8 mmol), Ac2O (14.0 mL, 148 mmol) and triethyl orthoformate (8.25 mL, 49.6 mmol) was heated at 120 0C for 2 h. The mixture was concentrated in vacuo and dried under high vacuum. The crude product was dissolved in anhydrous toluene (120 mL) and [l-(aminomethyl)- cyclopropyl]]methanol (2.51 g, 24.8 mmol) was added very slowly at 0 0C. The reaction mixture was stirred at room temperature for 3h, and the solvent was removed by evaporation. The crude product was purified by column chromatography (Hexane : EtOAc 2:1) to yield the title compound (7.30 g, 75%) as a pale yellow solid. Mp. 74.5 -76.O0C. 1H-NMR(400 MHZ, CDCl3) delta 0.57-0.63 (4H, m), 1.12 (3H, t, J = 7.3 Hz), 1.62 (2H, t, J = 5.5 Hz), 3.50 (2H, d, J = 5.5 Hz), 3.98-4.17 (2H, m), 8.17 (IH, d, J = 5.5 Hz), <n="138"/>11.22 (IH, brs). EIMS (+) 393 [M] +. Anal. Calcd for Ci7H16F5NO4: C, 51.80; H, 3.90

Reference： [1]Patent: WO2009/35684,2009,A1 .Location in patent: Page/Page column 136-137

13
[ 45434-02-4 ]
[ 94695-50-8 ]
[ 122-51-0 ]
[ 1132814-37-9 ]

Yield	Reaction Conditions	Operation in experiment
94%		A solution of ethyl 3-oxo-3-(2,3,4,5-tetrafluorophenyl)propionate (7.93 g, 30.0 mmol), Ac2O (17.0 mL, 180 mmol) and triethyl orthoformate (10.0 mL, 60.1 mmol) was heated at 120 0C for 3 hours. The mixture was concentrated in vacuo and dried under high vacuum. The crude product was dissolved in anhydrous tolene (120 mL) and [l-(aminomethyl)-cyclopropyl]] methanol (3.04 g, 30.1 mmol) was added very slowly at 0 0C. The ration mixture was stirred at room temperature for 3 hours, and the solvent was removed by evaporation. The crude product was purified by column chromatography (Hexane : EtOAc 1 : 1) to yield the title compound (10.5 g, 94%) as a pale yellow solid. 1H NMR (400 MHz, CDCl3) delta 0.50-0.70 (4H, m), 0.97, 1.10 (each t, J = 7.3Hz, total 3H), <n="100"/>1.66 (IH, t, J = 4.9 Hz), 3.47 (2H, d, J - 6.1 Hz), 3.56 (2H, d, J = 4.9 Hz), 4.01-4.09 (2H m), 6.96-7.13 (IH, m), 8.06-8.12 (IH, m), 9.71, 11.1 (each br, total IH). ESIMS (+):375[M+H].

Reference： [1]Patent: WO2009/35684,2009,A1 .Location in patent: Page/Page column 98-99

14
[ 1206529-20-5 ]
[ 1206529-18-1 ]
[ 45434-02-4 ]
C₃₂H₂₆ClF₃N₄O₆ [ No CAS ]
C₃₂H₂₆BrF₃N₄O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In N,N-dimethyl-formamide at 150℃; for 0.333333h; Microwave irradiation;	152 EXAMPLE 152; Microwave treatment (150° C., 1200 sec) of A8 (154.5 mg, 0.258 mmol) and (1-aminomethyl-cyclopropyl)-methanol (132.6.4 mg, 1.311 mmol) in 2.5 mL of DMF was followed by the addition of hydrazine (0.1 mL, 102 mg, 3.2 mmol) and additional microwave treatment (150° C., 1200 sec) afforded crude product. Isolation and purification were accomplished via preparative HPLC to afford 41.8 mg of the product of this example (as a TFA salt).1H NMR (400 MHz, CH3OH-d4) d 7.90 (s, 1H), 7.33 (m, 2H), 7.15 (m, 2H), 4.77 (t, J=11.7 Hz, 2H), 4.11 (s, 2H), 3.97 (t, J=12.3 Hz, 2H), 3.60 (s, 2H), 3.52 (s, 2H), 0.66 (m, 2H), 0.61 (m, 2H).19F NMR (376 MHz, CH3OH-d4) d -73.115 (s, TFA), -103.897 (m), -113.543 (m)MS [M+1]=489.08.

Reference： [1]Current Patent Assignee: GILEAD SCIENCES INC - US2010/22508, 2010, A1 Location in patent: Page/Page column 109

15
[ 45434-02-4 ]
C₂₂H₂₂N₂O₃ [ No CAS ]
[ 1289647-94-4 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃;

Reference： [1]Location in patent: scheme or table Cowley, Phillip M.; Baker, James; Buchanan, Kirsteen I.; Carlyle, Ian; Clark, John K.; Clarkson, Thomas R.; Deehan, Maureen; Edwards, Darren; Kiyoi, Yasuko; Martin, Iain; Osbourn, Dawn; Walker, Glenn; Ward, Nick; Wishart, Grant [Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 7, p. 2034 - 2039]

16
[ 45434-02-4 ]
[ 1311369-25-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: dichloromethane / 40 h / 20 °C 1.2: 0.17 h 2.1: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 60 h / 20 °C 3.1: trifluoroacetic acid / dichloromethane / 2 h / 20 °C 3.2: pH 7 4.1: potassium carbonate; triethylamine / ethanol / 18 h / 20 - 80 °C 5.1: sodium hydroxide; water / ethanol / 2 h / 80 °C

Reference： [1]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - WO2011/71716, 2011, A1

17
[ 45434-02-4 ]
[ 1311369-22-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: dichloromethane / 40 h / 20 °C 1.2: 0.17 h 2.1: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 60 h / 20 °C

Reference： [1]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - WO2011/71716, 2011, A1

18
[ 45434-02-4 ]
[ 1311369-23-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: dichloromethane / 40 h / 20 °C 1.2: 0.17 h 2.1: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 60 h / 20 °C 3.1: trifluoroacetic acid / dichloromethane / 2 h / 20 °C 3.2: pH 7

Reference： [1]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - WO2011/71716, 2011, A1

19
[ 45434-02-4 ]
[ 1311369-24-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: dichloromethane / 40 h / 20 °C 1.2: 0.17 h 2.1: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 60 h / 20 °C 3.1: trifluoroacetic acid / dichloromethane / 2 h / 20 °C 3.2: pH 7 4.1: potassium carbonate; triethylamine / ethanol / 18 h / 20 - 80 °C

Reference： [1]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - WO2011/71716, 2011, A1

20
[ 3697-69-6 ]
[ 45434-02-4 ]

Yield	Reaction Conditions	Operation in experiment
	With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; for 4h;	S.1 Intermediate S: l'-oxo-2',3'-dihydro-l'H-spiro[cyclopropane-1,4'-[1,4]diazepino[1,2- a]indole]-8'-carboxylic acid Step 1: Synthesis of [l-(aminomethyl)cyclopropyl]methanol To a suspension of lithium aluminum hydride (34 g, 899 mmol) in THF (400 mL) is added a solution of ethyl l-(cyanomethyl)cyclopropanecarboxylate (25 g, 179 mmol) in THF (100 mL) at 0 °C. The reaction mixture is stirred at room temperature for 4 h. The reaction mixture is cooled to 0 °C and ice cold water (60 mL) is added. The mixture is extracted with EtOAc (2 X 300 mL). The organic layers are combined, dried (Na2S04) and concentrated to afford the title crude compound (20 g) which is used in the next step without purification.

Reference： [1]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - WO2011/71716, 2011, A1 Location in patent: Page/Page column 76

21
[ 45434-02-4 ]
[ 1943-67-5 ]
[ 1325738-93-9 ]

Yield	Reaction Conditions	Operation in experiment
43%	With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;	1 Step 1. A solution of (l-(aminomethyl)cyclopropyl)methanol (65 mg, 0.64 mmol) and l-tert-butyl-4-isocyanatobenzene (111 mg, 0.64 mmol) and DIPEA (250 mg, 1.92 mmol) in dry DCM (5 mL) was stirred at room temperature overnight, then MeOH (5 mL) was added and concentrated to give crude product, which was purified by prep-TLC (DCM : MeOH = 20 : 1) to afford pure 164 (750 mg, yield 43%) as white solid. ESI-MS (m/z):277.7 [M+l]+.

Reference： [1]Current Patent Assignee: EPIZYME, INC. - WO2012/82436, 2012, A2 Location in patent: Page/Page column 136-137

22
[ 45434-02-4 ]
[ 1381761-25-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / dichloromethane / 20 °C 2: 2-iodoxybenzoic acid / ethyl acetate / 2 h / Reflux

Reference： [1]Current Patent Assignee: EPIZYME, INC. - WO2012/82436, 2012, A2

23
[ 45434-02-4 ]
[ 1381761-26-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: N-ethyl-N,N-diisopropylamine / dichloromethane / 20 °C 2: 2-iodoxybenzoic acid / ethyl acetate / 2 h / Reflux 3: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 20 °C

Reference： [1]Current Patent Assignee: EPIZYME, INC. - WO2012/82436, 2012, A2

24
[ 45434-02-4 ]
[ 1381761-27-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 20 °C 2.1: 2-iodoxybenzoic acid / ethyl acetate / 2 h / Reflux 3.1: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 20 °C 4.1: trifluoroacetic acid / trifluoroacetic acid / 1 h / 20 °C 4.2: basic resin / 0.5 h / 20 °C

Reference： [1]Current Patent Assignee: EPIZYME, INC. - WO2012/82436, 2012, A2

25
[ 45434-02-4 ]
[ 5794-88-7 ]
[ 1411982-52-9 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 5-Bromo-2-aminobenzoic acid With 1,1'-carbonyldiimidazole In dichloromethane at 20℃; for 0.25h; Stage #2: (1-(aminomethyl)cyclopropyl)methanol In dichloromethane at 20℃;	180 Example 180; 3-((1-(hydroxymethyl)cyclopropyl)methyl)-6-(4-(trifluoromethoxy)phenyl)quinazolin-4(3H)-one (Compound IV-27) To a round bottom flask was added 2-amino-5-bromobenzoic acid (6.94 mmole), and CDI or EDCI-HCl (1.5 equiv) in CH2Cl2 (100 mL) and the mixture was stirred at RT for 15 min before addition of amine (1.4 equiv). The resulting reaction mixture was stirred at RT overnight. The mixture was washed with H2O and the organic extract was dried over Na2SO4 and then concentrated down under reduced pressure before purification by biotage column chromatography eluting with 5% methanol methylene chloride mixture to afford 1.35 grams of Compound 180-A.

Reference： [1]Current Patent Assignee: GILEAD SCIENCES INC - US2012/289493, 2012, A1 Location in patent: Page/Page column 110-111

26
[ 45434-02-4 ]
[ 5794-88-7 ]
[ 1411982-53-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: 1,1'-carbonyldiimidazole / dichloromethane / 0.25 h / 20 °C 1.2: 20 °C 2.1: ethanol / 100 °C

Reference： [1]Current Patent Assignee: GILEAD SCIENCES INC - US2012/289493, 2012, A1

27
[ 98730-77-9 ]
[ 45434-02-4 ]

Yield	Reaction Conditions	Operation in experiment
	With lithium aluminium tetrahydride In tetrahydrofuran at 45℃; for 18h;	38.1 First Step Lithium aluminum hydride (3.91 g, 103 mmol, 2 eq) was dissolved in tetrahydrofuran (100 mL), and compound 38a (5.00 g, 51.5 mmol, 3.37 mL, 1 eq) was added. The mixed solution was allowed to react at 45° C. for 18 hours. After completion of the reaction, water (4.00 mL), 15% NaOH (4.00 mL), and water (8.00 mL) were sequentially added at 0-20° C. to terminate the reaction. The mixture was stirred for 0.5 hour, filtered, and subjected to rotary evaporation under reduced pressure to give 38b. MS-ESI calculated for [M+H]+:102, found: 102.

Reference： [1]Current Patent Assignee: WUXI APPTEC CO., LTD. - US2020/339568, 2020, A1 Location in patent: Paragraph 0384-0386

28
[ 70214-59-4 ]
[ 45434-02-4 ]
C₁₆H₁₉NO [ No CAS ]
C₁₆H₁₉NO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In dimethyl sulfoxide at 20℃; for 0.5h;

Reference： [1]Gvozdev; Shavrin; Nefedov [Russian Chemical Bulletin, 2014, vol. 63, # 2, p. 409 - 415][Izvestiya Akademii Nauk. Seriya Khimicheskaya, 2014, vol. 2, p. 409 - 415,7]

29
[ 45434-02-4 ]
[ 197963-29-4 ]
(E)-6'-benzylidene-8',8'-dimethylhexahydrospiro[cyclopropane-1,3'-pyrrolo[2,1-b][1,3]oxazine] [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	Stage #1: (1-(aminomethyl)cyclopropyl)methanol; 2,2-dimethyl-5-phenylpent-4-ynal In dimethyl sulfoxide at 20℃; for 0.5h; Stage #2: With potassium hydroxide In dimethyl sulfoxide at 20℃; for 2h; stereoselective reaction;

Reference： [1]Gvozdev; Shavrin; Nefedov [Russian Chemical Bulletin, 2014, vol. 63, # 2, p. 409 - 415][Izvestiya Akademii Nauk. Seriya Khimicheskaya, 2014, vol. 2, p. 409 - 415,7]

30
[ 45434-02-4 ]
[ 197963-29-4 ]
C₁₈H₂₃NO [ No CAS ]
C₁₈H₂₃NO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In dimethyl sulfoxide at 20℃; for 0.5h;

Reference： [1]Gvozdev; Shavrin; Nefedov [Russian Chemical Bulletin, 2014, vol. 63, # 2, p. 409 - 415][Izvestiya Akademii Nauk. Seriya Khimicheskaya, 2014, vol. 2, p. 409 - 415,7]

31
[ 45434-02-4 ]
(2S,3R)-2-azido-N-(3-fluoro-2-(2-((S)-1-(phenylsulfonyl)aziridin-2-yl)ethyl)phenyl)-3-(4-fluorophenyl)-3-(tetrahydro-2H-pyran-4-yl)propanamide [ No CAS ]
(2S,3R)-2-azido-N-(3-fluoro-2-((S)-4-(((1-(hydroxymethyl)cyclopropyl)methyl)amino)-3-(phenylsulfonamido)butyl)phenyl)-3-(4-fluorophenyl)-3-(tetrahydro-2H-pyran-4-yl)propanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In 1,2-dichloro-ethane at 60℃; for 16h;	20.1 Step 1. (2S, 3R)-2-azido-N-(3-fluoro-2-((S)-4-(((l -(hydroxymethyl)cyclopropyl)methyl)amino)- 3-(phenylsulfonamido)butyl)phenyl)-3-(4-fluorophenyl)-3-(tetrahydro-2H-pyran-4- yl)propanamide. To a stirred solution of (25, 3R)-2-Azido-N-(3-fluoro-2-(2-((S)- l - (phenylsulfonyl)aziridin-2-yl)ethyl)phenyl)-3-(4-fluorophenyl)-3-(tetrahydro-2H-pyran-4- yl)propanamide (Step 3, Example 7) (0.25 g, 0.35 mmol) in 1 ,2-dichloroethane (4 mL) was added (l -(aminomethyl)cyclopropyl)methanol (2.47 g, 2.204 mmol) and the solution was heated to 60 °C for 16 h. The reaction mixture was cooled to room temperature and diluted with water (50 mL) and extracted with EtOAc (100 mL). The organic layer was washed with water (50 mL), brine (50 mL), dried (Na2S04), filtered and concentrated under reduced pressure. The yellow gum (0.30 g, crude) obtained was taken forward to the next step without further purification
	In 1,2-dichloro-ethane at 60℃; for 16h;	20.1 Step 1. (25, 3R)-2-azido-N-(3-fluoro-2-((5)-4-(((l-(hydroxymethyl)cyclopropyl)methyl)amino)- 3-(phenylsulfonamido)butyl)phenyl)-3-(4-fluorophenyl)-3-(tetrahydro-2H-pyran-4- yl)propanamide Step 1. (25, 3R)-2-azido-N-(3-fluoro-2-((5)-4-(((l-(hydroxymethyl)cyclopropyl)methyl)amino)- 3-(phenylsulfonamido)butyl)phenyl)-3-(4-fluorophenyl)-3-(tetrahydro-2H-pyran-4- yl)propanamide. To a stirred solution of (25, 3R)-2-Azido-N-(3-fluoro-2-(2-((5)-l- (phenylsulfonyl)aziridin-2-yl)ethyl)phenyl)-3-(4-fluorophenyl)-3-(tetrahydro-2H-pyran-4- yl)propanamide (Step 3, Example 7) (0.25 g, 0.35 mmol) in 1,2-dichloroethane (4 mL) was added (l-(aminomethyl)cyclopropyl)methanol (2.47 g, 2.204 mmol) and the solution was heated to 60 °C for 16 h. The reaction mixture was cooled to room temperature and diluted with water (50 mL) and extracted with EtOAc (100 mL). The organic layer was washed with water (50 mL), brine (50 mL), dried (Na2S04), filtered and concentrated under reduced pressure. The yellow gum (0.30 g, crude) obtained was taken forward to the next step without further purification.

Reference： [1]Current Patent Assignee: MERCK & CO INC; SCHULZ JUERGEN - WO2015/13835, 2015, A1 Location in patent: Page/Page column 154
[2]Current Patent Assignee: MERCK & CO INC; SCHULZ JUERGEN - WO2015/17393, 2015, A2 Location in patent: Page/Page column 141

32
[ 45434-02-4 ]
(2S,3S)-2-azido-N-(3-fluoro-2-(2-((S)-1-(phenylsulfonyl)aziridin-2-yl)ethyl)phenyl)-3-(4-fluorophenyl)-3-(6-methoxypyridin-3-yl)propanamide [ No CAS ]
((2S,3S)-2-azido-3-(4-chlorophenyl)-N-(3-fluoro-2-((S)-4-(((1-hydroxymethyl)cyclopropyl)methyl)amino)-3-(phenylsulfonamido)butyl)phenyl)-3-(6-methoxypyridin-3-yl)propanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In 1,2-dichloro-ethane at 60℃; for 16h;	19.4 Step 4. (2S, 35)-2-Azido-3-(4-chlorophenyl)-N-(3-fluoro-2-((5)-4-(((l - hydroxymethyl)cyclopropyl)methyl)amino)-3-(phenylsulfonamido)butyl)phenyl)-3-(6- methoxypyridin-3 -yl)propanamide To a stirred solution of (2S, 3S)-2-azido-3-(4-chlorophenyl)-N-(3-fluoro-2-(2-((S)- l-(phenylsulfonyl)aziridin-2-yl)ethyl)phenyl)-3-(6-methoxypyridin-3-yl)propanamide (0.200 g, 0.314 mmol) in 1 ,2-dichloroethane (8 mL) was added (l -(aminomethyl)cyclopropyl)methanol (0.222 g, 2.204 mmol) and the solution was heated to 60 °C for 16 h. The reaction mixture was cooled to room temperature and diluted with water (50 mL) and extracted with EtOAc (100 mL). The organic layer was washed with water (50 mL), brine (50 mL), dried (Na2S04), filtered and concentrated under reduced pressure. The yellow gum (0.192 g, crude) obtained was taken forward to the next step without purification. LC MS: M+H = 736.
	In 1,2-dichloro-ethane at 60℃; for 16h;	19.4 Step 4. (25,35)-2-Azido-3-(4-chlorophenyl)-N-(3-fluoro-2-((5)-4-(((l- hydroxymethyl)cyclopropyl)methyl)amino)-3-(phenylsulfonamido)butyl)phenyl)-3-(6- methoxypyridin-3-yl)propanamide Step 4. (25,35)-2-Azido-3-(4-chlorophenyl)-N-(3-fluoro-2-((5)-4-(((l- hydroxymethyl)cyclopropyl)methyl)amino)-3-(phenylsulfonamido)butyl)phenyl)-3-(6- methoxypyridin-3-yl)propanamide To a stirred solution of ( 5,,35,)-2-azido-3-(4-chloro henyl)-N-(3-fluoro-2-(2-((5,)- l-(phenylsulfonyl)aziridin-2-yl)ethyl)phenyl)-3-(6-methoxypyridin-3-yl)propanamide (0.200 g, 0.314 mmol) in 1,2-dichloroethane (8 mL) was added (l-(aminomethyl)cyclopropyl)methanol (0.222 g, 2.204 mmol) and the solution was heated to 60 °C for 16 h. The reaction mixture was cooled to room temperature and diluted with water (50 mL) and extracted with EtOAc (100 mL). The organic layer was washed with water (50 mL), brine (50 mL), dried (Na2S04), filtered and concentrated under reduced pressure. The yellow gum (0.192 g, crude) obtained was taken forward to the next step without purification. LC MS: M+H = 736.

Reference： [1]Current Patent Assignee: MERCK & CO INC; SCHULZ JUERGEN - WO2015/13835, 2015, A1 Location in patent: Page/Page column 150; 151
[2]Current Patent Assignee: MERCK & CO INC; SCHULZ JUERGEN - WO2015/17393, 2015, A2 Location in patent: Page/Page column 137; 138

33
[ 45434-02-4 ]
N-((1-(((tert-butyldimethylsilyl)oxy)methyl)-2-(p-tolyl)cyclopropyl)methyl)-1,1,1-trifluoromethanesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: triethylamine / dichloromethane / 0 - 20 °C 2.1: triethylamine / dichloromethane / 0.08 h / -78 °C 2.2: -78 °C 3.1: palladium diacetate; t-Boc-L-valine; silver carbonate; sodium 2,2,2-trifluoroacetate / <i>tert</i>-butyl alcohol / 18 h / 80 °C / Sealed tube

Reference： [1]Chan, Kelvin S. L.; Fu, Hai-Yan; Yu, Jin-Quan [Journal of the American Chemical Society, 2015, vol. 137, # 5, p. 2042 - 2046]

34
[ 45434-02-4 ]
N-((1-(((tert-butyldimethylsilyl)oxy)methyl)cyclopropyl)methyl)-1,1,1-trifluoromethanesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: triethylamine / dichloromethane / 0 - 20 °C 2.1: triethylamine / dichloromethane / 0.08 h / -78 °C 2.2: -78 °C

Reference： [1]Chan, Kelvin S. L.; Fu, Hai-Yan; Yu, Jin-Quan [Journal of the American Chemical Society, 2015, vol. 137, # 5, p. 2042 - 2046]

35
[ 45434-02-4 ]
[ 18162-48-6 ]
[ 737790-49-7 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In dichloromethane at 0 - 20℃;

Reference： [1]Chan, Kelvin S. L.; Fu, Hai-Yan; Yu, Jin-Quan [Journal of the American Chemical Society, 2015, vol. 137, # 5, p. 2042 - 2046]

36
[ 45434-02-4 ]
tert-butyl N-({5-ethyl-1-[(4-fluorophenyl)methyl]-1H-imidazol-2-yl}methyl)-N-[(4-formyl-6-methylpyridin-2-yl)methyl]carbamate [ No CAS ]
tert-butyl N-({5-ethyl-1-[(4-fluoro phenyl)methyl]-1H-imidazol-2-yl}methyl)-N-[(6-methyl-4-{5-oxa-7-azaspiro[2.5]octan-6-yl}pyridin-2-yl)methyl]carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In 1,2-dichloro-ethane at 20℃; for 3h;	[00654j Tert-butyl N-({5-ethyl-1-[(4-fluoro phenyl)methyl]-JH-imidazol-2-yl}methyl)-N-[(6- met hyl-4-{5-oxa- 7-azaspiro[2. 5]octan-6-yl}pyridin-2-yl)methyl]carbamate A mixture of tert-butyl N-( {5 -ethyl-i - [(4-fluorophenyl)methyl] -1 H-imidazol-2-yl} methyl)-N- [(4- formyl-6-methylpyridin-2-yl)methyl]carbamate and [1 -(aminomethyl)cyclopropyl]methanol in 1,2- dichloroethane was stirred at room temperature for 3 hour and concentrated to afford the titlecompound. ‘H-NMR (300 MHz, CDC13): ö 7.08-6.92 (m, 3H), 7.90-6.70 (m, 5H), 5.28 (s, 2H), 4.72 (s, 2H), 4.46 (s, 2H), 4.08 (d, 1H), 3.74 (d, 1H), 3.24-2.95 (m, 2H), 2.54 (s, 3H), 2.36 (q, 2H), 1.42-1.07 (m, 12H), 0.78-0.57 (m, 2H), 0.52-0.29 (m, 2H)ppm.

Reference： [1]Current Patent Assignee: GILEAD SCIENCES INC - WO2016/33169, 2016, A1 Location in patent: Paragraph 00654

37
[ 45434-02-4 ]
tert-butyl N-[3-(benzyloxy)-6-methoxypyridin-2-yl]methyl}-N-[(6-[(tert-butyldimethylsilyl)oxy]methyl}-4-formylpyridin-2-yl)methyl]carbamate [ No CAS ]
tert-butyl N-[3-(benzyloxy)-6-methoxypyridin-2-yl]methyl}-N-[(6-[(tert-butyldimethylsilyl)oxy]methyl}-4-{5-oxa-7-azaspiro[2.5]octan-6-yl}pyridin-2-yl)methyl]carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In 1,2-dichloro-ethane at 20℃; for 3h;	[00660j Tert-butyl N-[3- (benzyloxy)-6-methoxypyridin-2-yl]methyl}-N-[(6-[(tert- butyldimethylsilyl)oxy]methyl}-4-{5-oxa- 7-azaspiro[2. 5]octan-6-yl}pyridin-2-yl)methyl]carbamate A mixture of tert-butyl N- { [3 -(benzyloxy)-6-methoxypyridin-2-yl]methyl} -N- [(6- { [(tertbutyldimethylsilyl)oxy]methyl} -4-formylpyridin-2-yl)methyl] carbamate and [1- (aminomethyl)cyclopropyl]methanol in 1,2- dichioroethane was stirred at room temperature for 3 hour and concentrated to afford the title compound as colorless oil as a 1:1 mixture of closed form (title compound) and opened form (imine). ‘H-NMR (300 MHz, CDC13): ö 8.19 (s, 0.5H), 7.66 (d, 0.5H), 7.52 (d, 0.5H), 7.44 (s, 0.5H), 7.39-7.28 (m, 5.5H), 7.17-7.11 (m, 1H), 6.56-6.51 (m, 1H), 5.18 (d, 0.5H), 5.00-4.96 (m, 2H), 4.81-4.75 (m, 3H), 4.73-4.69 (m, 1H), 4.65-4.61 (m, 1H), 4.58-4.52 (m, 1H),4.24 (d, 0.5H), 3.89 (s, 1.5H), 3.88 (s, 1.5H), 3.67-3.64 (m, 2H), 3.47 (d, 0.5H), 3.36 (d, 0.5H), 2.42 (d, 0.5H), 1.44-1.36 (m, 9H), 0.97 (s, 4.5H), 0.96 (s, 4.5H), 0.66-0.34 (m, 4H), 0.13 (s, 3H), 0.11 (s, 3H) ppm.

Reference： [1]Current Patent Assignee: GILEAD SCIENCES INC - WO2016/33169, 2016, A1 Location in patent: Paragraph 00660

38
[ 45434-02-4 ]
tert-butyl N-({5-ethyl-1-[(4-fluorophenyl)methyl]-1H-imidazol-2-yl}methyl)-N-({6-methyl-4-[7-(trifluoroacetyl)-5-oxa-7-azaspiro[2.5]octan-6-yl]pyridin-2-yl}methyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1,2-dichloro-ethane / 3 h / 20 °C 2: trifluoroacetic anhydride / 1,2-dichloro-ethane / 5 h / 20 °C

Reference： [1]Current Patent Assignee: GILEAD SCIENCES INC - WO2016/33169, 2016, A1

39
[ 45434-02-4 ]
1-[6-(2-[({5-ethyl-1-[(4-fluorophenyl)methyl]-1H-imidazol-2-yl}methyl)amino]methyl}-6-methyl pyridin-4-yl)-5-oxa-7-azaspiro[2.5]octan-7-yl]-2,2,2-trifluoroethan-1-one trifluoroacetic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 1,2-dichloro-ethane / 3 h / 20 °C 2: trifluoroacetic anhydride / 1,2-dichloro-ethane / 5 h / 20 °C 3: 20 °C

Reference： [1]Current Patent Assignee: GILEAD SCIENCES INC - WO2016/33169, 2016, A1

40
[ 45434-02-4 ]
[ 501-53-1 ]
benzyl [1-(hydroxymethyl)cyclopropyl]methyl}carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
3 g	With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; Cooling with ice;	13.1 [Step 1] Preparation of benzyl [1-(hydroxymethyl)cyclopropyl]methyl}carbamate To a solution of [1-(aminomethyl)cyclopropyl]methanol (1.5 g) (which was prepared analogous to the method described in, for example, ) in dichloromethane (30 mL) was added DIPEA (3.7 g), benzyl chloroformate (3.5 g) was added thereto under ice cooling, and the mixture was stirred at room temperature overnight. The reaction solution was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (3.0 g). 1H-NMR (CDCl3) δ: 0.46 (4H, s), 2.78 (1H, t), 3.20 (2H, d), 3.40 (2H, d), 5.12 (2H, s), 5.23 (1H, s), 7.35-7.37 (5H, m)

Reference： [1]Current Patent Assignee: NIPPON SHINYAKU CO LTD - EP3190116, 2017, A1 Location in patent: Paragraph 0135

41
[ 45434-02-4 ]
C₁₇H₁₇F₂N₅O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: N-ethyl-N,N-diisopropylamine / dichloromethane / 20 °C / Cooling with ice 2: copper(l) iodide / acetonitrile / 1 h / 50 °C 3: methanol; 20% palladium hydroxide-activated charcoal 4: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1.5 h / 80 °C

Reference： [1]Current Patent Assignee: NIPPON SHINYAKU CO LTD - EP3190116, 2017, A1

42
[ 45434-02-4 ]
C₁₄H₁₇F₂NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / dichloromethane / 20 °C / Cooling with ice 2: copper(l) iodide / acetonitrile / 1 h / 50 °C

Reference： [1]Current Patent Assignee: NIPPON SHINYAKU CO LTD - EP3190116, 2017, A1

43
[ 45434-02-4 ]
N-[1-({6-[({1-[(difluoromethoxy)methyl]cyclopropyl}methyl)amino]-2-(pyrazolo[5,1-b][1,3]thiazol-7-yl)pyrimidin-4-yl}carbonyl)piperidin-4-yl]cyclopropanecarboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 20 °C / Cooling with ice 2.1: copper(l) iodide / acetonitrile / 1 h / 50 °C 3.1: methanol; 20% palladium hydroxide-activated charcoal 4.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1.5 h / 80 °C 5.1: water; lithium hydroxide monohydrate / tetrahydrofuran 5.2: 20 °C

Reference： [1]Current Patent Assignee: NIPPON SHINYAKU CO LTD - EP3190116, 2017, A1

44
[ 45434-02-4 ]
{1-[(difluoromethoxy)methyl]cyclopropyl}methanamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: N-ethyl-N,N-diisopropylamine / dichloromethane / 20 °C / Cooling with ice 2: copper(l) iodide / acetonitrile / 1 h / 50 °C 3: methanol; 20% palladium hydroxide-activated charcoal

Reference： [1]Current Patent Assignee: NIPPON SHINYAKU CO LTD - EP3190116, 2017, A1

45
[ 45434-02-4 ]
1-(2-methylbiphenyl-3-yl)piperidin-4-one [ No CAS ]
[ 76-05-1 ]
(1-((1-(2-methylbiphenyl-3-yl)piperidin-4-ylamino)methyl)cyclopropyl)methanol trifluoroacetate trifluoroacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: (1-(aminomethyl)cyclopropyl)methanol; 1-(2-methylbiphenyl-3-yl)piperidin-4-one With acetic acid In N,N-dimethyl-formamide at 20℃; for 0.0833333h; Stage #2: With sodium cyanoborohydride In N,N-dimethyl-formamide at 20℃; Stage #3: trifluoroacetic acid In water; acetonitrile	26.4 Step 4: (I -((I -(2-methylbiphenyl-3-yUpiperidin-4-ylamino)methyUcyclopropyUmethanol To a stirred solution of 1-(2-methylbiphenyl-3-yl)piperidin-4-one (10 mg, 0.04mmol) in N,N-dimethylformamide (1.0 mL), [1-(aminomethyl)cyclopropyl]methanol (5.6mg, 0.055 mmol) and acetic acid (6.2 11L, 0.11 mmol) were added sequentially at roomtemperature. After 5 minutes, sodium cyanoborohydride (6.9 mg, 0.11 mmol) was added. The10 resulting mixture was stirred at room temperature overnight. The volatiles were removedunder reduced pressure and the residue was purified on prep-HPLC (pH= 2,acetonitrile/water+TFA) to give the desired product as its TFA salt. LC-MS calculated forCnH31N20 [M+Ht m/z: 351.2; found: 351.3.

Reference： [1]Current Patent Assignee: INCYTE CORP - WO2017/205464, 2017, A1 Location in patent: Page/Page column 66

46
[ 45434-02-4 ]
3-(5-(5-((1H-indazol-5-yl)carbamoyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidin-4-yl)-2-fluorophenyl)propanoic acid [ No CAS ]
4-(4-fluoro-3-(3-(((1-(hydroxymethyl)cyclopropyl)methyl)amino)-3-oxopropyl)phenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide for 16h;

Reference： [1]Waldschmidt, Helen V.; Bouley, Renee; Kirchhoff, Paul D.; Lee, Pil; Tesmer, John J.G.; Larsen, Scott D. [Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 9, p. 1507 - 1515]

47
[ 45434-02-4 ]
N-({1-[(4-fluorophenoxy)methyl]cyclopropyl}methyl)-N,2-dimethyl-5-phenyl-1,3-thiazole-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; triethylamine / N,N-dimethyl-formamide / 0.17 h / 150 °C / Microwave irradiation 2: di-isopropyl azodicarboxylate; triphenylphosphine / dichloromethane / 72 h / 20 °C 3: sodium hydride / N,N-dimethyl-formamide / 1 h

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2006/110626, 2006, A1

48
[ 45434-02-4 ]
N-({1-[(4-fluorophenoxy)methyl]cyclopropyl}methyl)-2-methyl-5-phenyl-1,3-thiazole-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; triethylamine / N,N-dimethyl-formamide / 0.17 h / 150 °C / Microwave irradiation 2: di-isopropyl azodicarboxylate; triphenylphosphine / dichloromethane / 72 h / 20 °C

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2006/110626, 2006, A1

49
[ 45434-02-4 ]
(2-bromo-6,7-dihydrothiazolo[5,4-c]pyridin-5(4H)-yl)(1H-indol-2-yl)methanone [ No CAS ]
[1-([5-(1H-indole-2-carbonyl)-4H,5H,6H,7H-[1,3]thiazolo[5 ,4-c]pyridin-2-yl]amino}methyl)cyclopropyl]methanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%	at 60℃; for 72h;	87 [1 -( { [5-( 1 H-indole-2-carbonyl)-4H,5H,6H,7H-[ 1 ,3]thiazolo [5 ,4-c]pyridin-2- yl] amino } methyl)cyclopropyl]methanol To (2-bromo-6,7-dihydrothiazolo[5,4-cjpyridin-5(4H)-yl)( 1 H-indol-2-yl)methanone (0.030 g,0.083 mmol) was added (1-(aminomethyl)cyclopropyl)methanol (0.653 ml, 6.87 mmol). Themixture was stirred at 60°C for 72h. DMSO (2 mL) was added, and the mixture purified by acidic reverse phase HPLC (twice) to give the desired product (0.0 149 g, 47% yield)Rt (Method A) 3.00 mins, m/z 383 [M+H].

Reference： [1]Current Patent Assignee: AICURIS GMBH & CO. KG - WO2019/86141, 2019, A1 Location in patent: Page/Page column 167

50
[ 45434-02-4 ]
O-phenyl {3,5-difluoro-4-[(3-[1-(trifluoromethyl)cyclobutyl]-1-[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]phenyl}carbamothioate [ No CAS ]
N-{3,5-difluoro-4-[(3-[1-(trifluoromethyl)cyclobutyl]-1-[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]phenyl}-N'-[1-(hydroxymethyl)cyclopropyl]methyl}thiourea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	In N,N-dimethyl-formamide at 60℃;	Intermediate 19 N-{3,5-difluoro-4-[(3-[1 -(trifluoromethyl)cyclobutyl]-1 -[2-(trimethylsilyl)ethoxy]methyl}- 1 H-pyrrolo[2,3-b]pyridin-4-yl)oxy]phenyl}-N'-[1 - (hydroxymethyl)cyclopropyl]methyl}thiourea O-phenyl {3,5-difluoro-4-[(3-[1 -(trifluoromethyl)cyclobutyl]-1 -[2-(trimethylsilyl)ethoxy]nnethyl}-1 H-pyrrolo[2,3-b]pyridin-4-yl)oxy]phenyl}carbamothioate (Intermediate 14, 190 mg, 292 pmol) and 1 -(aminomethyl)cyclopropyl]methanol (59.2 mg, 585 pmol, CAS No. [45434-02-4]) were dissolved in N,N-dimethylformamide (1 ml_) and stirred overnight at 60°C. The solvent was removed under vacuum, and the crude was purified by silica gel chromatography to yield the title compound (228 mg, quantitative). LC-MS (Method 4): Rt = 1 .59 min; MS (ESIpos): m/z = 657 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) d [ppm]: 10.00 (s, 1 H), 8.16 (d, 1 H), 8.10 (m, 1 H), 7.77 (s, 1 H), 7.59 (m, 2H), 6.38 (m, 1 H), 5.62 (s, 2H), 4.78 (br t, 1 H), 3.57-3.48 (m, 4H), 3.35 (m, 2H), 2.71 -2.62 (m, 4H), 2.08-1 .90 (m, 2H), 0.80 (t, 2H), 0.50 (m, 2H), 0.44 (m, 2H), -0.1 1 (s, 9H).

Reference： [1]Current Patent Assignee: Helmholtz Association - WO2020/120257, 2020, A1 Location in patent: Page/Page column 65

51
[ 45434-02-4 ]
C₁₄H₁₀N₂O₂S₃ [ No CAS ]
(Z)-2-(((1-(hydroxymethyl)cyclopropyl)methyl) amino)-5-((2-(2-hydroxy phenyl)thiazol-4-yl)methylene)thiazol-4(5H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25 mg	With N-ethyl-N,N-diisopropylamine In ethanol at 140℃; for 0.333333h; Sealed tube; Microwave irradiation;	General procedure: A3: To a solution of the appropriate methylated TTZD (1 eq.) in EtOH (1.5 mL) was added the requisite amine (1.5 eq.) and diisopropylethyl amine (2.5 eq.). The vial was sealed and heated in a microwave at 140 °C for 20 min. The reaction was cooled to room temperature, diluted with water and left to stand at room temperature until a precipitate formed, which was filtered, washed with water, ice-cooled EtOH and Et2O. The solid was collected and dried under vacuum to give the desired product.

Reference： [1]Quevedo, Camilo E.; Bataille, Carole J.R.; Byrne, Simon; Durbin, Matthew; Elkins, Jon; Guillermo, Abigail; Jones, Alan M.; Knapp, Stefan; Nadali, Anna; Walker, Roderick G.; Wilkinson, Isabel V.L.; Wynne, Graham M.; Davies, Stephen G.; Russell, Angela J. [Bioorganic and Medicinal Chemistry, 2020, vol. 28, # 22]

52
[ 45434-02-4 ]
C₁₅H₉F₃N₂O₂S₃ [ No CAS ]
(Z)-2-(((1-(hydroxymethyl)cyclopropyl)methyl) amino)-5-((2-(4-(trifluoromethoxy)phenyl)thiazol-4-yl)methylene)thiazol-4(5H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61 mg	With N-ethyl-N,N-diisopropylamine In ethanol at 140℃; for 0.333333h; Sealed tube; Microwave irradiation;	General procedure: A3: To a solution of the appropriate methylated TTZD (1 eq.) in EtOH (1.5 mL) was added the requisite amine (1.5 eq.) and diisopropylethyl amine (2.5 eq.). The vial was sealed and heated in a microwave at 140 °C for 20 min. The reaction was cooled to room temperature, diluted with water and left to stand at room temperature until a precipitate formed, which was filtered, washed with water, ice-cooled EtOH and Et2O. The solid was collected and dried under vacuum to give the desired product.

53
[ 45434-02-4 ]
8’-bromo-2’,3‘-dihydro-1‘H,5‘H-spiro[cyclopropane-1,4’-pyrrolo[1,2-a][1,4]diazepin]-1’-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / 20 °C 2: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 0 - 20 °C / Inert atmosphere 3: trifluoroacetic acid / 2 h / 20 °C 4: potassium carbonate; triethylamine / methanol / 20 °C

Reference： [1]Current Patent Assignee: HUTCHISON CHINA MEDITECH LTD.; HUTCHISON MEDIPHARMA LTD - WO2020/244637, 2020, A1

54
[ 45434-02-4 ]
C₁₁H₁₅BrN₂O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / 20 °C 2: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 0 - 20 °C / Inert atmosphere 3: trifluoroacetic acid / 2 h / 20 °C

Reference： [1]Current Patent Assignee: HUTCHISON CHINA MEDITECH LTD.; HUTCHISON MEDIPHARMA LTD - WO2020/244637, 2020, A1

55
[ 24424-99-5 ]
[ 45434-02-4 ]
methyl 4-bromo-1-((1-(((tert-butoxycarbonyl)amino)methyl)cyclopropyl)methyl)-1H-pyrrole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / 20 °C 2: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 0 - 20 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: HUTCHISON CHINA MEDITECH LTD.; HUTCHISON MEDIPHARMA LTD - WO2020/244637, 2020, A1

56
[ 45434-02-4 ]
[ 79-04-9 ]
C₇H₁₂ClNO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate In dichloromethane at 20℃; for 1h;	38.2 Second Step Compound 38b (4 g, 39.6 mmol, 1 eq) was dissolved in dichloromethane (10.0 mL), sodium carbonate (8.38 g, 79.1 mmol, 2 eq) and compound 38c (4.47 g, 39.6 mmol, 3.15 mL, 1.0 eq) were added. The mixed solution was allowed to react at 20° C. for an hour. After completion of the reaction, the reaction solution was subjected to rotary evaporation under reduced pressure to dryness, and purified by column chromatography (20% methanol/dichloromethane) to give compound 38d. MS-ESI calculated for [M+H]+: 178, found: 178. 1H NMR (400 MHz, CDCl3) δ: 7.27 (s, 1H), 4.09 (s, 2H), 3.44 (d, J=5.2 Hz, 2H), 3.32 (d, J=5.6 Hz, 2H), 2.83-2.81 (m, 1H), 0.52 (d, J=3.6 Hz, 4H).

Reference： [1]Current Patent Assignee: WUXI APPTEC CO., LTD. - US2020/339568, 2020, A1 Location in patent: Paragraph 0387-0389

57
[ 45434-02-4 ]
C₇H₁₁NO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium carbonate / dichloromethane / 1 h / 20 °C 2: sodium hydride / tetrahydrofuran; mineral oil / 1 h / 20 °C

Reference： [1]Current Patent Assignee: WUXI APPTEC CO., LTD. - US2020/339568, 2020, A1

58
[ 45434-02-4 ]
5-oxa-8-azaspiro[2.6]nonane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: sodium carbonate / dichloromethane / 1 h / 20 °C 2: sodium hydride / tetrahydrofuran; mineral oil / 1 h / 20 °C 3: lithium aluminium tetrahydride / tetrahydrofuran / 1 h / 20 °C

Reference： [1]Current Patent Assignee: WUXI APPTEC CO., LTD. - US2020/339568, 2020, A1

59
[ 45434-02-4 ]
C₂₆H₃₀N₆O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: sodium carbonate / dichloromethane / 1 h / 20 °C 2: sodium hydride / tetrahydrofuran; mineral oil / 1 h / 20 °C 3: lithium aluminium tetrahydride / tetrahydrofuran / 1 h / 20 °C 4: N-ethyl-N,N-diisopropylamine / dimethyl sulfoxide / 16 h / 70 °C

Reference： [1]Current Patent Assignee: WUXI APPTEC CO., LTD. - US2020/339568, 2020, A1

60
[ 45434-02-4 ]
C₂₇H₃₂N₆O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: sodium carbonate / dichloromethane / 1 h / 20 °C 2: sodium hydride / tetrahydrofuran; mineral oil / 1 h / 20 °C 3: lithium aluminium tetrahydride / tetrahydrofuran / 1 h / 20 °C 4: N-ethyl-N,N-diisopropylamine / dimethyl sulfoxide / 16 h / 70 °C

Reference： [1]Current Patent Assignee: WUXI APPTEC CO., LTD. - US2020/339568, 2020, A1

61
[ 45434-02-4 ]
C₃₈H₄₉N₇O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: potassium carbonate / acetonitrile / 15 h / 20 °C 2.1: sodium t-butanolate / tetrahydrofuran / 0.5 h / -20 °C / Inert atmosphere 2.2: 0.33 h / -20 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: JACOBIO PHARMACEUTICALS GROUP CO LTD - WO2021/23247, 2021, A1

62
[ 45434-02-4 ]
C₃₆H₄₃N₇O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: potassium carbonate / acetonitrile / 15 h / 20 °C 2.1: sodium t-butanolate / tetrahydrofuran / 0.5 h / -20 °C / Inert atmosphere 2.2: 0.33 h / -20 °C / Inert atmosphere 3.1: trifluoroacetic acid / dichloromethane / 3 h / 25 °C 3.2: 0.67 h / 25 °C

Reference： [1]Current Patent Assignee: JACOBIO PHARMACEUTICALS GROUP CO LTD - WO2021/23247, 2021, A1

63
[ 110-52-1 ]
[ 45434-02-4 ]
[ 1174666-14-8 ]

Yield	Reaction Conditions	Operation in experiment
183mg	With potassium carbonate In acetonitrile at 20℃; for 15h;

Reference： [1]Current Patent Assignee: JACOBIO PHARMACEUTICALS GROUP CO LTD - WO2021/23247, 2021, A1 Location in patent: Page/Page column 46

64
[ 45434-02-4 ]
3,5-difluoro-4-((5-iodo-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine-4-yl)oxy)aniline [ No CAS ]
1-(3,5-difluoro-4-((5-(2-fluoro-4-methoxyphenyl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy)phenyl)-3-((1-(hydroxymethyl)cyclopropyl)methyl)thiourea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	Stage #1: 3,5-difluoro-4-((5-iodo-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine-4-yl)oxy)aniline With 1,1'-Thiocarbonyldi-2(1H)-pyridone In dichloromethane at 40℃; for 1h; Inert atmosphere; Stage #2: (1-(aminomethyl)cyclopropyl)methanol In dichloromethane at 20℃; for 3h; Inert atmosphere;	3 1-(3,5-Difluoro-4-((5-(2-fluoro-4-methoxyphenyl)-7-((2-(trimethylsilyl)ethoxy)methyl) -7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxo)phenyl)-3-((1-(hydroxymethyl)cyclopropyl)methyl)thiourea At room temperature, 3,5-difluoro-4-((5-(2-fluoro-4-methoxyphenyl)-7-((2- (Trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxo)aniline (150 mg, 0.29 mmol) in anhydrous dichloride Methane (3.0ml)Add 1,1'-thiocarbonyl bis(pyridine-2(1H)-one) to the solution(74 mg, 0.32 mmol), replaced with argon three times, and then the reaction solution was placed in a 40 degree oil bath and stirred for 1 hour. After the conversion of the raw materials was completed, the reaction solution was cooled to room temperature, and then (1-(aminomethyl)cyclopropyl)methanol (59 mg, 0.58 mmol) was added. The reaction was stirred at room temperature for 3 hours. The reaction was checked by LCMS. The solvent was concentrated under reduced pressure to obtain crude oil, which was separated by reverse C-18 silica gel column (HCOOH) to obtain white solid 1-(3,5-difluoro-4-((5-(2-fluoro-4-methoxyphenyl) )-7-((2-(Trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxo)phenyl)-3- ((1-(hydroxymethyl)cyclopropyl)methyl)thiourea (180 mg, yield: 94%).

Reference： [1]Current Patent Assignee: ENNOVABIO ZHEJIANG PHARMACEUTICALS; SHANGHAI ENNOVABIO PHARMACEUTICALS; ENNOVABIO ZHEJIANG PHARMACEUTICAL - CN113354648, 2021, A Location in patent: Paragraph 0169-0173

65
[ 45434-02-4 ]
3,5-difluoro-4-((5-(trifluoromethyl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy)aniline [ No CAS ]
1-(3,5-difluoro-4-((5-(trifluoromethyl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy)phenyl)-3-((1-(hydroxymethyl)cyclopropyl)methyl)thiourea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88.4%	Stage #1: 3,5-difluoro-4-((5-(trifluoromethyl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy)aniline With 1,1'-Thiocarbonyldi-2(1H)-pyridone In dichloromethane at 40℃; for 1h; Inert atmosphere; Stage #2: (1-(aminomethyl)cyclopropyl)methanol In dichloromethane at 20℃; for 1h; Inert atmosphere;	6 1-(3,5-Difluoro-4-((5-(trifluoromethyl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[ 2,3-d)pyrimidin-4-yl)oxo)phenyl)-3-((1-(hydroxymethyl)cyclopropyl)methyl)thiourea At room temperature, add to a 10 ml round bottom flask equipped with a magnetic stirrer3,5-Difluoro-4-((5-(trifluoromethyl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3 -d]pyrimidin-4-yl)oxo)aniline (252 mg, 0.55 mmol)Anhydrous dichloromethane (4.0 ml)Add 1,1'-thiocarbonyl bis(pyridine-2(1H)-one) (140 mg, 0.60 mmol) to the solution,The argon gas was replaced three times, and then the reaction solution was placed in a 40 degree oil bath and stirred for 1 hour. After the conversion of the raw materials was completed, the reaction solution was cooled to room temperature, and then (1-(aminomethyl)cyclopropyl)methanol (111 mg, 1.09 mmol) was added. The reaction was stirred at room temperature for 1 hour. The reaction was checked by LCMS. The solvent was concentrated under reduced pressure to obtain crude oil, which was separated by reverse C-18 silica gel column (HCOOH) to obtain white solid 1-(3,5-difluoro-4-((5-(trifluoromethyl)-7-(( 2-(Trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxo)phenyl)-3-((1-(hydroxyl (Methyl)cyclopropyl)methyl)thiourea (292 mg, yield: 88.4%).

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H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 45434-02-4 ] {[proInfo.proName]}

Quality Control of [ 45434-02-4 ]

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[ 45434-02-4 ] Synthesis Path-Downstream 1~65

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Aliphatic Cyclic Hydrocarbons

Alcohols

Amines

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[ 45434-02-4 ]